<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/NCT02193074</url>
  </required_header>
  <id_info>
    <org_study_id>ISIS 396443-CS3B</org_study_id>
    <secondary_id>2013-004422-29</secondary_id>
    <nct_id>NCT02193074</nct_id>
  </id_info>
  <brief_title>A Study to Assess the Efficacy and Safety of Nusinersen (ISIS 396443) in Infants With Spinal Muscular Atrophy</brief_title>
  <acronym>ENDEAR</acronym>
  <official_title>A Phase 3, Randomized, Double-Blind, Sham-Procedure Controlled Study to Assess the Clinical Efficacy and Safety of ISIS 396443 Administered Intrathecally in Patients With Infantile-onset Spinal Muscular Atrophy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Biogen</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Biogen</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of the study is to examine the clinical efficacy of nusinersen (ISIS&#xD;
      396443) administered intrathecally (IT) to participants with infantile-onset with&#xD;
      infantile-onset spinal muscular atrophy (SMA). The secondary objective of the study is to&#xD;
      examine the safety and tolerability of nusinersen administered intrathecally to participants&#xD;
      with infantile-onset SMA.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study was conducted and the protocol was registered by Ionis Pharmaceuticals, Inc..&#xD;
&#xD;
      In August 2016, sponsorship of the trial was transferred to Biogen.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    After a positive interim analysis, the decision was made to terminate the study early to allow&#xD;
    for participants to enroll into an open label study&#xD;
  </why_stopped>
  <start_date type="Actual">August 19, 2014</start_date>
  <completion_date type="Actual">November 21, 2016</completion_date>
  <primary_completion_date type="Actual">November 21, 2016</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>Yes</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Motor Milestones Responders</measure>
    <time_frame>assessed at the later of the Day 183, Day 302, or Day 394 study visits</time_frame>
    <description>The definition of a motor milestones responder was based on improvement in the motor milestones categories in Section 2 of the Hammersmith Infant Neurological Examination (HINE), with the exclusion of voluntary grasp, as follows:&#xD;
(i) subject demonstrates ≥ 2-point increase in the motor milestones category of ability to kick or achievement of maximal score on that category (touching toes), or a 1-point increase in the motor milestones category of head control, rolling, sitting, crawling, standing, or walking, and (ii) among the motor milestone categories, with the exclusion of voluntary grasp, there are more categories where there is improvement as defined in (i) than worsening. (For the category of ability to kick, worsening is defined as ≥ 2-point decrease or decrease to the lowest possible score of no kicking. For the other categories, worsening is defined as ≥ 1-point decrease.) The lowest possible score for the HINE is 0 (zero), and the highest possible score for the HINE is 28.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to Death or Permanent Ventilation</measure>
    <time_frame>Day 91, Day 182, Day 273, Day 364, Day 394</time_frame>
    <description>Estimated proportion of participants who died or required permanent ventilation by a given study day, based on the Kaplan-Meier product-limit method. Time to death or permanent ventilation was defined as either tracheostomy or ≥ 16 hours ventilation/day continuously for &gt; 21 days in the absence of an acute reversible event. This endpoint was adjudicated by a blinded, independent group of experienced clinicians, the Event Adjudication Committee (EAC), based on review of clinical study data and supporting information. Results are based on all available data.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) Responders</measure>
    <time_frame>assessed at Baseline and the later of the Day 183, Day 302, or Day 394 study visits</time_frame>
    <description>A participants was considered a CHOP-INTEND responder if the change from baseline in CHOP-INTEND total score is ≥ 4 points based on assessment at the later of the Day 183, Day 302, or Day 394 study visits. CHOP-INTEND tests includes 16 items structured to move from easiest to hardest with the grading including gravity eliminated (lower scores) to antigravity movements (higher scores). Total scores range from 0 to 64, with higher scores indicating better movement functioning. Results are based on all available data.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Summary of Time to Death</measure>
    <time_frame>Day 91, Day 182, Day 273, Day 364, Day 394</time_frame>
    <description>Estimated proportion of participants who died by given duration thresholds, based on the Kaplan-Meier product-limit method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Not Requiring Permanent Ventilation</measure>
    <time_frame>Up to Day 394</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Compound Muscular Action Potential (CMAP) Responders</measure>
    <time_frame>assessed at the later of the Day 183, Day 302, or Day 394 study visits</time_frame>
    <description>CMAP is an electrophysiological technique that can be used to determine the approximate number of motor neurons in a muscle or group of muscles. A participant was defined as a CMAP responder if the CMAP amplitude at the peroneal nerve was increasing to or maintained at ≥ 1 mV (comparing to the baseline) based on assessment at the later of the Day 183, Day 302, or Day 394 study visits. Results are based on all available data.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Death or Permanent Ventilation in the Subgroup of Participants Below the Study Median Disease Duration</measure>
    <time_frame>Day 91, Day 182, Day 273, Day 364, Day 394</time_frame>
    <description>Estimated proportion of participants who died or required permanent ventilation (EAC-adjudicated events) among participants below the study median disease duration (13.1 weeks), by given duration thresholds, based on the Kaplan-Meier product-limit method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Death or Permanent Ventilation in the Subgroup of Participants Above the Study Median Disease Duration</measure>
    <time_frame>Day 91, Day 182, Day 273, Day 364, Day 394</time_frame>
    <description>Estimated proportion of participants who died or required permanent ventilation (EAC-adjudicated events) among participants above the study median disease duration (13.1 weeks), by given duration thresholds, based on the Kaplan-Meier product-limit method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Experiencing Adverse Events (AEs), Serious AEs (SAEs) and Discontinuations Due to AEs</measure>
    <time_frame>Screening through Day 394 (± 7 days) or early termination</time_frame>
    <description>AE: any unfavorable and unintended sign, symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE is considered related to the investigational drug product. SAE: any AE that in the view of either the Investigator or Sponsor, meets any of the following criteria: results in death; is life threatening: that is, poses an immediate risk of death at the time of the event; requires in-patient hospitalization or prolongation of existing hospitalization; results in a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; results in congenital anomaly or birth defect in the offspring of the participant (whether male or female); is an important medical event in the opinion of the Investigator or Sponsor.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With AEs Corresponding to Changes in Hematology Values</measure>
    <time_frame>up to Day 394 (± 7 days) or early termination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With AEs Corresponding to Changes in Blood Chemistry Values</measure>
    <time_frame>up to Day 394 (± 7 days) or early termination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Meeting Selected Vital Sign Criteria Post-Baseline</measure>
    <time_frame>up to Day 394 (± 7 days) or early termination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Summary of Shifts in 12-lead Electrocardiogram (ECG) Results</measure>
    <time_frame>up to Day 394 (± 7 days) or early termination</time_frame>
    <description>Shift to 'abnormal, not clinically significant' includes 'unknown' or 'normal' to 'abnormal, not clinically significant'. Shift to 'abnormal, clinically significant' includes 'unknown' or 'normal' to 'abnormal, clinically significant'.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Clinically Significant Changes From Baseline in Urinalysis Values</measure>
    <time_frame>up to Day 394 (± 7 days) or early termination</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">122</enrollment>
  <condition>Spinal Muscular Atrophy</condition>
  <arm_group>
    <arm_group_label>nusinersen</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham procedure</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>nusinersen</intervention_name>
    <description>Administered by intrathecal (IT) injection as specified in the treatment arm.</description>
    <arm_group_label>nusinersen</arm_group_label>
    <other_name>ISIS 396443</other_name>
    <other_name>BIIB058</other_name>
    <other_name>Spinraza</other_name>
    <other_name>IONIS-SMN Rx</other_name>
    <other_name>ISIS SMNRx</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Sham procedure</intervention_name>
    <description>Small needle prick on the lower back at the location where the IT injection is normally made</description>
    <arm_group_label>Sham procedure</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Be born (gestational age) between 37 and 42 weeks&#xD;
&#xD;
          -  Be medically diagnosed with spinal muscular atrophy (SMA)&#xD;
&#xD;
          -  Have Survival Motor Neuron2 (SMN2) Copy number = 2&#xD;
&#xD;
          -  Body weight equal to or greater than 3rd percentile for age using appropriate&#xD;
             country-specific guidelines&#xD;
&#xD;
          -  Be able to follow all study procedures&#xD;
&#xD;
          -  Reside within approximately 9 hours ground-travel distance from a participating study&#xD;
             center, for the duration of the study&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Hypoxemia (oxygen [O2] saturation awake less than 96% or O2 saturation asleep less&#xD;
             than 96%, without ventilation support) during screening evaluation&#xD;
&#xD;
          -  Clinically significant abnormalities in hematology or clinical chemistry parameters or&#xD;
             Electrocardiogram (ECG), as assessed by the Site Investigator, at the Screening visit&#xD;
             that would render the participant unsuitable for participation in the study&#xD;
&#xD;
          -  Participant's parent or legal guardian is not willing to meet standard of care&#xD;
             guidelines (including vaccinations and respiratory syncytial virus prophylaxis if&#xD;
             available), nor provide nutritional and respiratory support throughout the study&#xD;
&#xD;
        NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>210 Days</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Biogen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UCLA Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</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 of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</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 University 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 Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke Children's Hospital</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Doernbecher Children's Hospital</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 - Neurology</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UT Southwestern Medical Center/Children's Medical Center Dallas</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75235</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Primary Children's Medical Center (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>Sydney Children's Hospital</name>
      <address>
        <city>Sydney</city>
        <state>New South Wales</state>
        <zip>2031</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Children's Hospital, Children's Neuroscience Centre</name>
      <address>
        <city>Parkville</city>
        <state>Victoria</state>
        <zip>3052</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Universitaire des Enfants Reine FABIOLA (HUDERF)</name>
      <address>
        <city>Brussels</city>
        <zip>15 - 1020</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>British Columbia Children's Hospital/UBC</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V6H 3N1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital for Sick Children</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 1X8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut de Myologie</name>
      <address>
        <city>Paris</city>
        <zip>75012</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitatsklinikum Essen</name>
      <address>
        <city>Essen</city>
        <zip>45147</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universtatsklinikum Freiburg, Zentrum fur Kinder-und Jugendmedizin , Abteilung Neuropadiatrie und Muskelerkrankungen</name>
      <address>
        <city>Freiburg</city>
        <zip>79106</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Giannina Gaslini, Centro Traslazionale di Miologia e Patologie Neurodegenerative</name>
      <address>
        <city>Genova</city>
        <zip>16148</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pediatric Neurology Unit, Catholic University</name>
      <address>
        <city>Rome</city>
        <zip>00153</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hyogo College of Medicine</name>
      <address>
        <city>Nishinomiya</city>
        <state>Hyogo</state>
        <zip>663-8131</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tokyo Women's Medical University</name>
      <address>
        <city>Tokyo</city>
        <zip>162-8666</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Vall d'Hebron</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario La Paz, Pediatric Neurology Department</name>
      <address>
        <city>Madrid</city>
        <zip>28046</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Gothenburg, The Queen Silvia Children's Hospital</name>
      <address>
        <city>Gothenburg</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hacettepe Children's Hospital</name>
      <address>
        <city>Ankara</city>
        <zip>06230</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCL Institute of Child Health/Great Ormond Street</name>
      <address>
        <city>London</city>
        <zip>WC1N 1EH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MRC Centre for Neuromuscular Diseases at Newcastle, Institute of Genetic Medicine Newcastle University</name>
      <address>
        <city>Newcastle</city>
        <zip>NE1 3BZ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Belgium</country>
    <country>Canada</country>
    <country>France</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Japan</country>
    <country>Korea, Republic of</country>
    <country>Spain</country>
    <country>Sweden</country>
    <country>Turkey</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Hong Kong</country>
    <country>Taiwan</country>
  </removed_countries>
  <link>
    <url>http://www.curesma.org</url>
    <description>Cure SMA</description>
  </link>
  <link>
    <url>http://mda.org/disease/spinal-muscular-atrophy</url>
    <description>Muscular Dystrophy Association</description>
  </link>
  <link>
    <url>https://www.rarediseases.org</url>
    <description>National Organization for Rare Diseases</description>
  </link>
  <link>
    <url>http://clinicalresearch.biogen.com/Content/Studies/CS3b%20Biogen.com%20Packet.pdf</url>
    <description>Clinical Study Report (CSR) Synopsis - a results summary</description>
  </link>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>July 14, 2014</study_first_submitted>
  <study_first_submitted_qc>July 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 17, 2014</study_first_posted>
  <results_first_submitted>May 16, 2017</results_first_submitted>
  <results_first_submitted_qc>June 29, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">July 28, 2017</results_first_posted>
  <last_update_submitted>February 12, 2021</last_update_submitted>
  <last_update_submitted_qc>February 12, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 17, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Spinal Muscular Atrophy</keyword>
  <keyword>SMA</keyword>
  <keyword>SMN</keyword>
  <keyword>SMNRx</keyword>
  <keyword>ISIS-SMNRx</keyword>
  <keyword>ISIS-SMN Rx</keyword>
  <keyword>ISIS 396443</keyword>
  <keyword>IONIS-SMNRx</keyword>
  <keyword>IONIS-SMN Rx</keyword>
  <keyword>Spinraza</keyword>
  <keyword>ENDEAR</keyword>
  <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>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Of the 149 participants screened, 27 were screening failures. A total of 122 participants enrolled and were randomized; 1 participant withdrew prior to receiving treatment.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Control</title>
          <description>Sham procedure administered on Study Days 1, 15, 29, 64, 183, and 302.</description>
        </group>
        <group group_id="P2">
          <title>Nusinersen</title>
          <description>Nusinersen (2.4 mg/mL) administered as an intrathecal (IT) lumbar puncture injection on Study Days 1, 15, 29, 64, 183, and 302.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="41">Randomized and received double-blind treatment.</participants>
                <participants group_id="P2" count="80">Randomized and received double-blind treatment.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>Completed During Follow-Up Period</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="26"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Completed Due to Early Study Termination</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="39"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
                <participants group_id="P2" count="65"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Control</title>
          <description>Sham procedure administered on Study Days 1, 15, 29, 64, 183, and 302.</description>
        </group>
        <group group_id="B2">
          <title>Nusinersen</title>
          <description>Nusinersen (2.4 mg/mL) administered as an IT lumbar puncture injection on Study Days 1, 15, 29, 64, 183, and 302.</description>
        </group>
        <group group_id="B3">
          <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="41"/>
            <count group_id="B2" value="80"/>
            <count group_id="B3" value="121"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <title>Age at Screening</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="164.7" spread="48.54"/>
                    <measurement group_id="B2" value="147.2" spread="46.85"/>
                    <measurement group_id="B3" value="153.1" spread="47.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Age at First Dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="180.5" spread="50.92"/>
                    <measurement group_id="B2" value="163.4" spread="49.57"/>
                    <measurement group_id="B3" value="169.2" spread="50.48"/>
                  </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="24"/>
                    <measurement group_id="B2" value="43"/>
                    <measurement group_id="B3" value="67"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="37"/>
                    <measurement group_id="B3" value="54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Motor Milestones Responders</title>
        <description>The definition of a motor milestones responder was based on improvement in the motor milestones categories in Section 2 of the Hammersmith Infant Neurological Examination (HINE), with the exclusion of voluntary grasp, as follows:&#xD;
(i) subject demonstrates ≥ 2-point increase in the motor milestones category of ability to kick or achievement of maximal score on that category (touching toes), or a 1-point increase in the motor milestones category of head control, rolling, sitting, crawling, standing, or walking, and (ii) among the motor milestone categories, with the exclusion of voluntary grasp, there are more categories where there is improvement as defined in (i) than worsening. (For the category of ability to kick, worsening is defined as ≥ 2-point decrease or decrease to the lowest possible score of no kicking. For the other categories, worsening is defined as ≥ 1-point decrease.) The lowest possible score for the HINE is 0 (zero), and the highest possible score for the HINE is 28.</description>
        <time_frame>assessed at the later of the Day 183, Day 302, or Day 394 study visits</time_frame>
        <population>Intent-to-treat population: all randomized participants who received ≥ 1 dose of study drug/sham procedure with Day 183, Day 302, or Day 394 data; the last available assessment was used. (Participants who died or withdrew from the study were counted as non-responders and were included in the denominator for the calculation of the percentages.)</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Sham procedure administered on Study Days 1, 15, 29, 64, 183, and 302.</description>
          </group>
          <group group_id="O2">
            <title>Nusinersen</title>
            <description>Nusinersen (2.4 mg/mL) administered as an IT lumbar puncture injection on Study Days 1, 15, 29, 64, 183, and 302.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Motor Milestones Responders</title>
          <description>The definition of a motor milestones responder was based on improvement in the motor milestones categories in Section 2 of the Hammersmith Infant Neurological Examination (HINE), with the exclusion of voluntary grasp, as follows:&#xD;
(i) subject demonstrates ≥ 2-point increase in the motor milestones category of ability to kick or achievement of maximal score on that category (touching toes), or a 1-point increase in the motor milestones category of head control, rolling, sitting, crawling, standing, or walking, and (ii) among the motor milestone categories, with the exclusion of voluntary grasp, there are more categories where there is improvement as defined in (i) than worsening. (For the category of ability to kick, worsening is defined as ≥ 2-point decrease or decrease to the lowest possible score of no kicking. For the other categories, worsening is defined as ≥ 1-point decrease.) The lowest possible score for the HINE is 0 (zero), and the highest possible score for the HINE is 28.</description>
          <population>Intent-to-treat population: all randomized participants who received ≥ 1 dose of study drug/sham procedure with Day 183, Day 302, or Day 394 data; the last available assessment was used. (Participants who died or withdrew from the study were counted as non-responders and were included in the denominator for the calculation of the percentages.)</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="73"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Fisher Exact</method>
            <param_type>Difference in percentages</param_type>
            <param_value>50.68</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>31.81</ci_lower_limit>
            <ci_upper_limit>66.48</ci_upper_limit>
            <estimate_desc>exact unconditional confidence interval</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Time to Death or Permanent Ventilation</title>
        <description>Estimated proportion of participants who died or required permanent ventilation by a given study day, based on the Kaplan-Meier product-limit method. Time to death or permanent ventilation was defined as either tracheostomy or ≥ 16 hours ventilation/day continuously for &gt; 21 days in the absence of an acute reversible event. This endpoint was adjudicated by a blinded, independent group of experienced clinicians, the Event Adjudication Committee (EAC), based on review of clinical study data and supporting information. Results are based on all available data.</description>
        <time_frame>Day 91, Day 182, Day 273, Day 364, Day 394</time_frame>
        <population>Intent-to-treat population: all randomized participants who received ≥ 1 dose of study drug/sham procedure and who died or required permanent ventilation.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Sham procedure administered on Study Days 1, 15, 29, 64, 183, and 302.</description>
          </group>
          <group group_id="O2">
            <title>Nusinersen</title>
            <description>Nusinersen (2.4 mg/mL) administered as an IT lumbar puncture injection on Study Days 1, 15, 29, 64, 183, and 302.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Death or Permanent Ventilation</title>
          <description>Estimated proportion of participants who died or required permanent ventilation by a given study day, based on the Kaplan-Meier product-limit method. Time to death or permanent ventilation was defined as either tracheostomy or ≥ 16 hours ventilation/day continuously for &gt; 21 days in the absence of an acute reversible event. This endpoint was adjudicated by a blinded, independent group of experienced clinicians, the Event Adjudication Committee (EAC), based on review of clinical study data and supporting information. Results are based on all available data.</description>
          <population>Intent-to-treat population: all randomized participants who received ≥ 1 dose of study drug/sham procedure and who died or required permanent ventilation.</population>
          <units>proportion of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
                <count group_id="O2" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>By Day 91 (13 weeks/3 months)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.268"/>
                    <measurement group_id="O2" value="0.240"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>By Day 182 (26 weeks/6 months)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.605"/>
                    <measurement group_id="O2" value="0.294"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>By Day 273 (39 weeks/9 months)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.702"/>
                    <measurement group_id="O2" value="0.404"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>By Day 364 (52 weeks/12 months)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.735"/>
                    <measurement group_id="O2" value="0.447"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>By Day 394 (13 months)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.735"/>
                    <measurement group_id="O2" value="0.447"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.0046</p_value>
            <method>Log Rank</method>
            <method_desc>Based on log-rank test stratified by disease duration.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.0164</p_value>
            <method>Cox proportional hazards model</method>
            <method_desc>Based on Cox proportional hazards model adjusted for each subject's disease duration at screening.</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.530</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.3156</ci_lower_limit>
            <ci_upper_limit>0.8902</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) Responders</title>
        <description>A participants was considered a CHOP-INTEND responder if the change from baseline in CHOP-INTEND total score is ≥ 4 points based on assessment at the later of the Day 183, Day 302, or Day 394 study visits. CHOP-INTEND tests includes 16 items structured to move from easiest to hardest with the grading including gravity eliminated (lower scores) to antigravity movements (higher scores). Total scores range from 0 to 64, with higher scores indicating better movement functioning. Results are based on all available data.</description>
        <time_frame>assessed at Baseline and the later of the Day 183, Day 302, or Day 394 study visits</time_frame>
        <population>Intent-to-treat population: all randomized participants who received ≥ 1 dose of study drug/sham procedure with Day 183, Day 302, or Day 394 data; the last available assessment was used. (Participants who died or withdrew from the study were counted as non-responders and were included in the denominator for the calculation of the percentages.)</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Sham procedure administered on Study Days 1, 15, 29, 64, 183, and 302.</description>
          </group>
          <group group_id="O2">
            <title>Nusinersen</title>
            <description>Nusinersen (2.4 mg/mL) administered as an IT lumbar puncture injection on Study Days 1, 15, 29, 64, 183, and 302.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) Responders</title>
          <description>A participants was considered a CHOP-INTEND responder if the change from baseline in CHOP-INTEND total score is ≥ 4 points based on assessment at the later of the Day 183, Day 302, or Day 394 study visits. CHOP-INTEND tests includes 16 items structured to move from easiest to hardest with the grading including gravity eliminated (lower scores) to antigravity movements (higher scores). Total scores range from 0 to 64, with higher scores indicating better movement functioning. Results are based on all available data.</description>
          <population>Intent-to-treat population: all randomized participants who received ≥ 1 dose of study drug/sham procedure with Day 183, Day 302, or Day 394 data; the last available assessment was used. (Participants who died or withdrew from the study were counted as non-responders and were included in the denominator for the calculation of the percentages.)</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="73"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Fisher Exact</method>
            <param_type>DIfference in percentages</param_type>
            <param_value>68.53</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>51.27</ci_lower_limit>
            <ci_upper_limit>81.99</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Summary of Time to Death</title>
        <description>Estimated proportion of participants who died by given duration thresholds, based on the Kaplan-Meier product-limit method.</description>
        <time_frame>Day 91, Day 182, Day 273, Day 364, Day 394</time_frame>
        <population>Intent-to-treat population: all randomized participants who received ≥ 1 dose of study drug/sham procedure and who died. Results are based on all available data.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Sham procedure administered on Study Days 1, 15, 29, 64, 183, and 302.</description>
          </group>
          <group group_id="O2">
            <title>Nusinersen</title>
            <description>Nusinersen (2.4 mg/mL) administered as an IT lumbar puncture injection on Study Days 1, 15, 29, 64, 183, and 302.</description>
          </group>
        </group_list>
        <measure>
          <title>Summary of Time to Death</title>
          <description>Estimated proportion of participants who died by given duration thresholds, based on the Kaplan-Meier product-limit method.</description>
          <population>Intent-to-treat population: all randomized participants who received ≥ 1 dose of study drug/sham procedure and who died. Results are based on all available data.</population>
          <units>proportion of particiants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>by Day 91</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.195"/>
                    <measurement group_id="O2" value="0.101"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>by Day 182</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.348"/>
                    <measurement group_id="O2" value="0.141"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>by Day 273</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.382"/>
                    <measurement group_id="O2" value="0.173"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>by Day 364</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.419"/>
                    <measurement group_id="O2" value="0.173"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>by Day 394</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.419"/>
                    <measurement group_id="O2" value="0.173"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.0041</p_value>
            <method>Log Rank</method>
            <method_desc>Based on log-rank test stratified by disease duration (primary analysis).</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.0082</p_value>
            <method>Cox proportional hazards</method>
            <method_desc>Based on Cox proportional hazards model adjusted for each subject's disease duration at screening (sensitivity analysis).</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.372</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.1787</ci_lower_limit>
            <ci_upper_limit>0.7745</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Not Requiring Permanent Ventilation</title>
        <time_frame>Up to Day 394</time_frame>
        <population>Intent-to-treat population: all randomized participants who received ≥ 1 dose of study drug/sham procedure.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Sham procedure administered on Study Days 1, 15, 29, 64, 183, and 302.</description>
          </group>
          <group group_id="O2">
            <title>Nusinersen</title>
            <description>Nusinersen (2.4 mg/mL) administered as an IT lumbar puncture injection on Study Days 1, 15, 29, 64, 183, and 302.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Not Requiring Permanent Ventilation</title>
          <population>Intent-to-treat population: all randomized participants who received ≥ 1 dose of study drug/sham procedure.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
                <count group_id="O2" value="80"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="68"/>
                    <measurement group_id="O2" value="77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Compound Muscular Action Potential (CMAP) Responders</title>
        <description>CMAP is an electrophysiological technique that can be used to determine the approximate number of motor neurons in a muscle or group of muscles. A participant was defined as a CMAP responder if the CMAP amplitude at the peroneal nerve was increasing to or maintained at ≥ 1 mV (comparing to the baseline) based on assessment at the later of the Day 183, Day 302, or Day 394 study visits. Results are based on all available data.</description>
        <time_frame>assessed at the later of the Day 183, Day 302, or Day 394 study visits</time_frame>
        <population>Intent-to-treat population: all randomized participants who received ≥ 1 dose of study drug/sham procedure with Day 183, Day 302, or Day 394 data; the last available assessment was used. (Participants who died or withdrew from the study were counted as non-responders and were included in the denominator for the calculation of the percentages.)</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Sham procedure administered on Study Days 1, 15, 29, 64, 183, and 302.</description>
          </group>
          <group group_id="O2">
            <title>Nusinersen</title>
            <description>Nusinersen (2.4 mg/mL) administered as an IT lumbar puncture injection on Study Days 1, 15, 29, 64, 183, and 302.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Compound Muscular Action Potential (CMAP) Responders</title>
          <description>CMAP is an electrophysiological technique that can be used to determine the approximate number of motor neurons in a muscle or group of muscles. A participant was defined as a CMAP responder if the CMAP amplitude at the peroneal nerve was increasing to or maintained at ≥ 1 mV (comparing to the baseline) based on assessment at the later of the Day 183, Day 302, or Day 394 study visits. Results are based on all available data.</description>
          <population>Intent-to-treat population: all randomized participants who received ≥ 1 dose of study drug/sham procedure with Day 183, Day 302, or Day 394 data; the last available assessment was used. (Participants who died or withdrew from the study were counted as non-responders and were included in the denominator for the calculation of the percentages.)</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="73"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.0004</p_value>
            <method>Fisher Exact</method>
            <param_type>Difference in percentages</param_type>
            <param_value>30.21</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>10.35</ci_lower_limit>
            <ci_upper_limit>48.09</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Death or Permanent Ventilation in the Subgroup of Participants Below the Study Median Disease Duration</title>
        <description>Estimated proportion of participants who died or required permanent ventilation (EAC-adjudicated events) among participants below the study median disease duration (13.1 weeks), by given duration thresholds, based on the Kaplan-Meier product-limit method.</description>
        <time_frame>Day 91, Day 182, Day 273, Day 364, Day 394</time_frame>
        <population>Intent-to-treat population: all randomized participants who received ≥ 1 dose of study drug/sham procedure and were below the study median disease duration.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Sham procedure administered on Study Days 1, 15, 29, 64, 183, and 302.</description>
          </group>
          <group group_id="O2">
            <title>Nusinersen</title>
            <description>Nusinersen (2.4 mg/mL) administered as an IT lumbar puncture injection on Study Days 1, 15, 29, 64, 183, and 302.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Death or Permanent Ventilation in the Subgroup of Participants Below the Study Median Disease Duration</title>
          <description>Estimated proportion of participants who died or required permanent ventilation (EAC-adjudicated events) among participants below the study median disease duration (13.1 weeks), by given duration thresholds, based on the Kaplan-Meier product-limit method.</description>
          <population>Intent-to-treat population: all randomized participants who received ≥ 1 dose of study drug/sham procedure and were below the study median disease duration.</population>
          <units>proportion of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>by Day 91</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.238"/>
                    <measurement group_id="O2" value="0.128"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>by Day 182</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.546"/>
                    <measurement group_id="O2" value="0.128"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>by Day 273</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.697"/>
                    <measurement group_id="O2" value="0.228"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>by Day 364</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.773"/>
                    <measurement group_id="O2" value="0.271"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>by Day 394</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.773"/>
                    <measurement group_id="O2" value="0.271"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.0003</p_value>
            <method>Log Rank</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.0014</p_value>
            <method>Cox proportional hazards</method>
            <method_desc>Based on Cox proportional hazards model adjusted for each subject's disease duration at screening.</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.240</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.1002</ci_lower_limit>
            <ci_upper_limit>0.5753</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Death or Permanent Ventilation in the Subgroup of Participants Above the Study Median Disease Duration</title>
        <description>Estimated proportion of participants who died or required permanent ventilation (EAC-adjudicated events) among participants above the study median disease duration (13.1 weeks), by given duration thresholds, based on the Kaplan-Meier product-limit method.</description>
        <time_frame>Day 91, Day 182, Day 273, Day 364, Day 394</time_frame>
        <population>Intent-to-treat population: all randomized participants who received ≥ 1 dose of study drug/sham procedure and were above the study median disease duration.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Sham procedure administered on Study Days 1, 15, 29, 64, 183, and 302.</description>
          </group>
          <group group_id="O2">
            <title>Nusinersen</title>
            <description>Nusinersen (2.4 mg/mL) administered as an IT lumbar puncture injection on Study Days 1, 15, 29, 64, 183, and 302.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Death or Permanent Ventilation in the Subgroup of Participants Above the Study Median Disease Duration</title>
          <description>Estimated proportion of participants who died or required permanent ventilation (EAC-adjudicated events) among participants above the study median disease duration (13.1 weeks), by given duration thresholds, based on the Kaplan-Meier product-limit method.</description>
          <population>Intent-to-treat population: all randomized participants who received ≥ 1 dose of study drug/sham procedure and were above the study median disease duration.</population>
          <units>proportion of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>by Day 91</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.300"/>
                    <measurement group_id="O2" value="0.350"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>by Day 182</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.670"/>
                    <measurement group_id="O2" value="0.462"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>by Day 273</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.725"/>
                    <measurement group_id="O2" value="0.584"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>by Day 364</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.725"/>
                    <measurement group_id="O2" value="0.625"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>by Day 394</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.725"/>
                    <measurement group_id="O2" value="0.625"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.3953</p_value>
            <method>Log Rank</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.6268</p_value>
            <method>Cox proportional hazards</method>
            <method_desc>Based on Cox proportional hazards model adjusted for each subject's disease duration at screening.</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.844</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.4270</ci_lower_limit>
            <ci_upper_limit>1.6698</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Experiencing Adverse Events (AEs), Serious AEs (SAEs) and Discontinuations Due to AEs</title>
        <description>AE: any unfavorable and unintended sign, symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE is considered related to the investigational drug product. SAE: any AE that in the view of either the Investigator or Sponsor, meets any of the following criteria: results in death; is life threatening: that is, poses an immediate risk of death at the time of the event; requires in-patient hospitalization or prolongation of existing hospitalization; results in a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; results in congenital anomaly or birth defect in the offspring of the participant (whether male or female); is an important medical event in the opinion of the Investigator or Sponsor.</description>
        <time_frame>Screening through Day 394 (± 7 days) or early termination</time_frame>
        <population>Safety Population: all subjects who received ≥ 1 dose of study drug/sham procedure.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Sham procedure administered on Study Days 1, 15, 29, 64, 183, and 302.</description>
          </group>
          <group group_id="O2">
            <title>Nusinersen</title>
            <description>Nusinersen (2.4 mg/mL) administered as an IT lumbar puncture injection on Study Days 1, 15, 29, 64, 183, and 302.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Experiencing Adverse Events (AEs), Serious AEs (SAEs) and Discontinuations Due to AEs</title>
          <description>AE: any unfavorable and unintended sign, symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE is considered related to the investigational drug product. SAE: any AE that in the view of either the Investigator or Sponsor, meets any of the following criteria: results in death; is life threatening: that is, poses an immediate risk of death at the time of the event; requires in-patient hospitalization or prolongation of existing hospitalization; results in a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; results in congenital anomaly or birth defect in the offspring of the participant (whether male or female); is an important medical event in the opinion of the Investigator or Sponsor.</description>
          <population>Safety Population: all subjects who received ≥ 1 dose of study drug/sham procedure.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
                <count group_id="O2" value="80"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Any event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40"/>
                    <measurement group_id="O2" value="77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Moderate or severe event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39"/>
                    <measurement group_id="O2" value="70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Severe event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33"/>
                    <measurement group_id="O2" value="45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Possibly related or related event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Related event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39"/>
                    <measurement group_id="O2" value="61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Related serious event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treatment discontinuation due to an event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                    <measurement group_id="O2" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With AEs Corresponding to Changes in Hematology Values</title>
        <time_frame>up to Day 394 (± 7 days) or early termination</time_frame>
        <population>Safety Population: all subjects who received ≥ 1 dose of study drug/sham procedure.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Sham procedure administered on Study Days 1, 15, 29, 64, 183, and 302.</description>
          </group>
          <group group_id="O2">
            <title>Nusinersen</title>
            <description>Nusinersen (2.4 mg/mL) administered as an IT lumbar puncture injection on Study Days 1, 15, 29, 64, 183, and 302.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With AEs Corresponding to Changes in Hematology Values</title>
          <population>Safety Population: all subjects who received ≥ 1 dose of study drug/sham procedure.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
                <count group_id="O2" value="80"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Anemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neutrophil count increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Leukocytosis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With AEs Corresponding to Changes in Blood Chemistry Values</title>
        <time_frame>up to Day 394 (± 7 days) or early termination</time_frame>
        <population>Safety Population: all subjects who received ≥ 1 dose of study drug/sham procedure.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Sham procedure administered on Study Days 1, 15, 29, 64, 183, and 302.</description>
          </group>
          <group group_id="O2">
            <title>Nusinersen</title>
            <description>Nusinersen (2.4 mg/mL) administered as an IT lumbar puncture injection on Study Days 1, 15, 29, 64, 183, and 302.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With AEs Corresponding to Changes in Blood Chemistry Values</title>
          <population>Safety Population: all subjects who received ≥ 1 dose of study drug/sham procedure.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
                <count group_id="O2" value="80"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Blood potassium decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Liver function test abnormal</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alanine aminotransferase increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Aspartate aminotransferase increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Blood chloride decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Blood iron decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Blood sodium decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>C-reactive protein increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypokalemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypoglycemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hyperglycemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Transaminases increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Meeting Selected Vital Sign Criteria Post-Baseline</title>
        <time_frame>up to Day 394 (± 7 days) or early termination</time_frame>
        <population>Safety Population: all subjects who received ≥ 1 dose of study drug/sham procedure and had an assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Sham procedure administered on Study Days 1, 15, 29, 64, 183, and 302.</description>
          </group>
          <group group_id="O2">
            <title>Nusinersen</title>
            <description>Nusinersen (2.4 mg/mL) administered as an IT lumbar puncture injection on Study Days 1, 15, 29, 64, 183, and 302.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Meeting Selected Vital Sign Criteria Post-Baseline</title>
          <population>Safety Population: all subjects who received ≥ 1 dose of study drug/sham procedure and had an assessment.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
                <count group_id="O2" value="80"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Systolic blood pressure &lt;90 mmHg</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36"/>
                    <measurement group_id="O2" value="74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Systolic blood pressure &gt;140 mmHg</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Systolic blood pressure &gt;160 mmHg</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Diastolic blood pressure &lt;50 mmHg</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26"/>
                    <measurement group_id="O2" value="71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Diastolic blood pressure &gt;90 mmHg</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Diastolic blood pressure &gt;100 mmHg</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pulse rate &lt;60 bpm</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pulse rate &gt;100 bpm</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41"/>
                    <measurement group_id="O2" value="80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Temperature &gt;38.0 C</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Temperature &lt;36.0 C</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                    <measurement group_id="O2" value="45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Respiratory rate &lt;12 breaths/min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Respiratory rate &gt;20 breaths/min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41"/>
                    <measurement group_id="O2" value="80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Body weight ≥7% decrease from BL</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Body weight ≥7% increase from BL</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33"/>
                    <measurement group_id="O2" value="67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Summary of Shifts in 12-lead Electrocardiogram (ECG) Results</title>
        <description>Shift to 'abnormal, not clinically significant' includes 'unknown' or 'normal' to 'abnormal, not clinically significant'. Shift to 'abnormal, clinically significant' includes 'unknown' or 'normal' to 'abnormal, clinically significant'.</description>
        <time_frame>up to Day 394 (± 7 days) or early termination</time_frame>
        <population>Safety Population: all subjects who received ≥ 1 dose of study drug/sham procedure and whose baseline value was not abnormal and who had at least one post-baseline value.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Sham procedure administered on Study Days 1, 15, 29, 64, 183, and 302.</description>
          </group>
          <group group_id="O2">
            <title>Nusinersen</title>
            <description>Nusinersen (2.4 mg/mL) administered as an IT lumbar puncture injection on Study Days 1, 15, 29, 64, 183, and 302.</description>
          </group>
        </group_list>
        <measure>
          <title>Summary of Shifts in 12-lead Electrocardiogram (ECG) Results</title>
          <description>Shift to 'abnormal, not clinically significant' includes 'unknown' or 'normal' to 'abnormal, not clinically significant'. Shift to 'abnormal, clinically significant' includes 'unknown' or 'normal' to 'abnormal, clinically significant'.</description>
          <population>Safety Population: all subjects who received ≥ 1 dose of study drug/sham procedure and whose baseline value was not abnormal and who had at least one post-baseline value.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="65"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Shift to abnormal, not clinically significant</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Shift to abnormal, clinically significant</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>From unknown to abnormal, clinically significant</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Clinically Significant Changes From Baseline in Urinalysis Values</title>
        <time_frame>up to Day 394 (± 7 days) or early termination</time_frame>
        <population>Safety Population: all subjects who received ≥ 1 dose of study drug/sham procedure.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Sham procedure administered on Study Days 1, 15, 29, 64, 183, and 302.</description>
          </group>
          <group group_id="O2">
            <title>Nusinersen</title>
            <description>Nusinersen (2.4 mg/mL) administered as an IT lumbar puncture injection on Study Days 1, 15, 29, 64, 183, and 302.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Clinically Significant Changes From Baseline in Urinalysis Values</title>
          <population>Safety Population: all subjects who received ≥ 1 dose of study drug/sham procedure.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
                <count group_id="O2" value="80"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Screening through Day 394 (± 7 days) or early termination</time_frame>
      <desc>Treatment-emergent events are presented.</desc>
      <group_list>
        <group group_id="E1">
          <title>Control</title>
          <description>Sham procedure administered on Study Days 1, 15, 29, 64, 183, and 302.</description>
        </group>
        <group group_id="E2">
          <title>Nusinersen</title>
          <description>Nusinersen (2.4 mg/mL) administered as an IT lumbar puncture injection on Study Days 1, 15, 29, 64, 183, and 302.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 18.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="39" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="61" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Cardio-respiratory arrest</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Cyanosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Gastric haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Retching</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Salivary hypersecretion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>General physical health deterioration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Surgical failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchiolitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Bronchitis viral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Candida sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Corona virus infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Ear infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Gastroenteritis rotavirus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection viral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Moraxella infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Pneumonia bacterial</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Pneumonia influenzal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Pneumonia moraxella</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Pneumonia parainfluenzae viral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Pneumonia pneumococcal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Pneumonia pseudomonal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Pneumonia respiratory syncytial viral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Pneumonia viral</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Pyelonephritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Respiratory syncytial virus bronchiolitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection viral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Rhinovirus infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Staphylococcal sepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Stoma site abscess</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Systemic infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Viral infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Viral upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Delayed recovery from anaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Feeding tube complication</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Femur fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Head injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Tracheal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Tracheal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Vaccination complication</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Body temperature increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Heart rate decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Medical observation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Oxygen saturation decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Respirovirus test positive</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Failure to thrive</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Feeding disorder of infancy or early childhood</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Feeding intolerance</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Weight gain poor</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Brain injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Hypoxic-ischaemic encephalopathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute respiratory distress syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Apnoea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Apparent life threatening event</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Aspiration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Atelectasis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Bronchial secretion retention</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Chronic respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Hypercapnia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Hypoventilation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Increased bronchial secretion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Lung disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Obstructive airways disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Pneumonia aspiration</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Respiratory arrest</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Respiratory disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Respiratory distress</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="20" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Respiratory tract congestion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Shock</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 18.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="35" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="70" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="28" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Salivary hypersecretion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Teething</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Oedema</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="24" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="43" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bacterial tracheitis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Bronchiolitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Candida infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Ear infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Oral candidiasis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Rhinovirus infection</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Stoma site infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="22" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Viral infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Viral upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Feeding tube complication</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Oxygen saturation decreased</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Scoliosis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Atelectasis</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Bronchial secretion retention</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Pneumonia aspiration</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Respiratory distress</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Sleep apnoea syndrome</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract congestion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Decubitus ulcer</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Dermatitis contact</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Dermatitis diaper</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="41"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="80"/>
              </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>Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Biogen Study Medical Director</name_or_title>
      <organization>Biogen</organization>
      <email>clinicaltrials@biogen.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/NCT02193074
org study id: ISIS 396443-CS3B
secondary id: 2013-004422-29
nct id: NCT02193074
lead sponsor: 
has dmc: Yes
The primary objective of the study is to examine the clinical efficacy of nusinersen (ISIS
      396443) administered intrathecally (IT) to participants with infantile-onset with
      infantile-onset spinal muscular atrophy (SMA). The secondary objective of the study is to
      examine the safety and tolerability of nusinersen administered intrathecally to participants
      with infantile-onset SMA.
This study was conducted and the protocol was registered by Ionis Pharmaceuticals, Inc..

      In August 2016, sponsorship of the trial was transferred to Biogen.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Percentage of Motor Milestones Responders
time frame: assessed at the later of the Day 183, Day 302, or Day 394 study visits
description: The definition of a motor milestones responder was based on improvement in the motor milestones categories in Section 2 of the Hammersmith Infant Neurological Examination (HINE), with the exclusion of voluntary grasp, as follows:
(i) subject demonstrates ≥ 2-point increase in the motor milestones category of ability to kick or achievement of maximal score on that category (touching toes), or a 1-point increase in the motor milestones category of head control, rolling, sitting, crawling, standing, or walking, and (ii) among the motor milestone categories, with the exclusion of voluntary grasp, there are more categories where there is improvement as defined in (i) than worsening. (For the category of ability to kick, worsening is defined as ≥ 2-point decrease or decrease to the lowest possible score of no kicking. For the other categories, worsening is defined as ≥ 1-point decrease.) The lowest possible score for the HINE is 0 (zero), and the highest possible score for the HINE is 28.
measure: Time to Death or Permanent Ventilation
time frame: Day 91, Day 182, Day 273, Day 364, Day 394
description: Estimated proportion of participants who died or required permanent ventilation by a given study day, based on the Kaplan-Meier product-limit method. Time to death or permanent ventilation was defined as either tracheostomy or ≥ 16 hours ventilation/day continuously for > 21 days in the absence of an acute reversible event. This endpoint was adjudicated by a blinded, independent group of experienced clinicians, the Event Adjudication Committee (EAC), based on review of clinical study data and supporting information. Results are based on all available data.
measure: Percentage of Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) Responders
time frame: assessed at Baseline and the later of the Day 183, Day 302, or Day 394 study visits
description: A participants was considered a CHOP-INTEND responder if the change from baseline in CHOP-INTEND total score is ≥ 4 points based on assessment at the later of the Day 183, Day 302, or Day 394 study visits. CHOP-INTEND tests includes 16 items structured to move from easiest to hardest with the grading including gravity eliminated (lower scores) to antigravity movements (higher scores). Total scores range from 0 to 64, with higher scores indicating better movement functioning. Results are based on all available data.
measure: Summary of Time to Death
time frame: Day 91, Day 182, Day 273, Day 364, Day 394
description: Estimated proportion of participants who died by given duration thresholds, based on the Kaplan-Meier product-limit method.
measure: Percentage of Participants Not Requiring Permanent Ventilation
time frame: Up to Day 394
measure: Percentage of Compound Muscular Action Potential (CMAP) Responders
time frame: assessed at the later of the Day 183, Day 302, or Day 394 study visits
description: CMAP is an electrophysiological technique that can be used to determine the approximate number of motor neurons in a muscle or group of muscles. A participant was defined as a CMAP responder if the CMAP amplitude at the peroneal nerve was increasing to or maintained at ≥ 1 mV (comparing to the baseline) based on assessment at the later of the Day 183, Day 302, or Day 394 study visits. Results are based on all available data.
measure: Time to Death or Permanent Ventilation in the Subgroup of Participants Below the Study Median Disease Duration
time frame: Day 91, Day 182, Day 273, Day 364, Day 394
description: Estimated proportion of participants who died or required permanent ventilation (EAC-adjudicated events) among participants below the study median disease duration (13.1 weeks), by given duration thresholds, based on the Kaplan-Meier product-limit method.
measure: Time to Death or Permanent Ventilation in the Subgroup of Participants Above the Study Median Disease Duration
time frame: Day 91, Day 182, Day 273, Day 364, Day 394
description: Estimated proportion of participants who died or required permanent ventilation (EAC-adjudicated events) among participants above the study median disease duration (13.1 weeks), by given duration thresholds, based on the Kaplan-Meier product-limit method.
measure: Number of Participants Experiencing Adverse Events (AEs), Serious AEs (SAEs) and Discontinuations Due to AEs
time frame: Screening through Day 394 (± 7 days) or early termination
description: AE: any unfavorable and unintended sign, symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE is considered related to the investigational drug product. SAE: any AE that in the view of either the Investigator or Sponsor, meets any of the following criteria: results in death; is life threatening: that is, poses an immediate risk of death at the time of the event; requires in-patient hospitalization or prolongation of existing hospitalization; results in a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; results in congenital anomaly or birth defect in the offspring of the participant (whether male or female); is an important medical event in the opinion of the Investigator or Sponsor.
measure: Number of Participants With AEs Corresponding to Changes in Hematology Values
time frame: up to Day 394 (± 7 days) or early termination
measure: Number of Participants With AEs Corresponding to Changes in Blood Chemistry Values
time frame: up to Day 394 (± 7 days) or early termination
measure: Number of Participants Meeting Selected Vital Sign Criteria Post-Baseline
time frame: up to Day 394 (± 7 days) or early termination
measure: Summary of Shifts in 12-lead Electrocardiogram (ECG) Results
time frame: up to Day 394 (± 7 days) or early termination
description: Shift to 'abnormal, not clinically significant' includes 'unknown' or 'normal' to 'abnormal, not clinically significant'. Shift to 'abnormal, clinically significant' includes 'unknown' or 'normal' to 'abnormal, clinically significant'.
measure: Number of Participants With Clinically Significant Changes From Baseline in Urinalysis Values
time frame: up to Day 394 (± 7 days) or early termination
arm group label: nusinersen
arm group type: Experimental
arm group label: Sham procedure
arm group type: Sham Comparator
intervention type: Drug
intervention name: nusinersen
description: Administered by intrathecal (IT) injection as specified in the treatment arm.
arm group label: nusinersen
other name: ISIS 396443
other name: BIIB058
other name: Spinraza
other name: IONIS-SMN Rx
other name: ISIS SMNRx
intervention type: Procedure
intervention name: Sham procedure
description: Small needle prick on the lower back at the location where the IT injection is normally made
arm group label: Sham procedure
criteria: 
gender: All
minimum age: N/A
maximum age: 210 Days
healthy volunteers: No
last name: Medical Director
role: Study Director
affiliation: Biogen
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country: Australia
country: Belgium
country: Canada
country: France
country: Germany
country: Italy
country: Japan
country: Korea, Republic of
country: Spain
country: Sweden
country: Turkey
country: United Kingdom
country: United States
country: Hong Kong
country: Taiwan
url: http://www.curesma.org
description: Cure SMA
url: http://mda.org/disease/spinal-muscular-atrophy
description: Muscular Dystrophy Association
url: https://www.rarediseases.org
description: National Organization for Rare Diseases
url: http://clinicalresearch.biogen.com/Content/Studies/CS3b%20Biogen.com%20Packet.pdf
description: Clinical Study Report (CSR) Synopsis - a results summary
responsible party type: Sponsor
mesh term: Muscular Atrophy
mesh term: Muscular Atrophy, Spinal
mesh term: Atrophy
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 