<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/NCT03277261</url>
  </required_header>
  <id_info>
    <org_study_id>TG1101-RMS301</org_study_id>
    <secondary_id>2017-000638-75</secondary_id>
    <nct_id>NCT03277261</nct_id>
  </id_info>
  <brief_title>Study to Assess the Efficacy and Safety of Ublituximab in Participants With Relapsing Forms of Multiple Sclerosis (RMS) ( ULTIMATE 1 )</brief_title>
  <acronym>ULTIMATE 1</acronym>
  <official_title>Phase III: UbLiTuximab In Multiple Sclerosis Treatment Effects (ULTIMATE I STUDY)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>TG Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>TG Therapeutics, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study determines the Annualized Relapse Rate (ARR) in participants with RMS after 96&#xD;
      weeks (approximately 2 years) treatment with intravenous (IV) infusion of ublituximab/oral&#xD;
      placebo compared to 14 mg oral teriflunomide/IV placebo.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 19, 2017</start_date>
  <completion_date type="Actual">November 6, 2020</completion_date>
  <primary_completion_date type="Actual">July 23, 2020</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Randomized, multi-center, double-blinded, active-controlled study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Double-blinded, active-controlled study</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Annualized Relapse Rate (ARR)</measure>
    <time_frame>Up to 96 weeks</time_frame>
    <description>ARR is defined as the number of Independent Relapse Adjudication Panel (IRAP)-confirmed relapses per participant year. The estimate of ARR for a treatment group is the total number of relapses for participants in the respective treatment group divided by the sum of treatment duration for participants in that specific treatment group.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Total Number of Gadolinium (Gd)-Enhancing T1-Lesions Per Magnetic Resonance Imaging (MRI) Scan Per Participant</measure>
    <time_frame>Weeks 12, 24, 48, and 96</time_frame>
    <description>The total number of Gd-enhancing T1-lesions were calculated as the sum of the individual number of lesions at Weeks 12, 24, 48, and 96, divided by the total number of MRI scans of the brain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Number of New and Enlarging T2 Hyperintense Lesions (NELs) Per MRI Scan Per Participant</measure>
    <time_frame>Weeks 24, 48, and 96</time_frame>
    <description>The total number of NELs were calculated as the sum of the individual number of lesions at Weeks 24, 48, and 96, divided by the total number of MRI scans of the brain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Confirmed Disability Progression (CDP) for at Least 12 Weeks</measure>
    <time_frame>Up to Week 96</time_frame>
    <description>12-week CDP is defined as an increase in EDSS at least 1 point higher than the baseline EDSS if the baseline EDSS is ≤5.5 or at least 0.5 higher than the baseline EDSS if the baseline EDSS is &gt;5.5. The EDSS is based on a standard neurological examination, (pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, and cerebral) and ambulation function system assessments. The EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death) where higher scores indicate disability. The time to onset of 12-week CDP is the time to progression to the EDSS change defined above.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With No Evidence of Disease Activity (NEDA)</measure>
    <time_frame>Week 24 up to Week 96</time_frame>
    <description>A participant with NEDA is defined as a participant without relapses confirmed by the IRAP, without MRI activities (no T1 Gd+ lesions and no new/enlarging T2 lesions), and no 12-week CDP. Any evidence of disease activity from Week 24 to Week 96 was counted as not reaching NEDA. Any evidence of disease activity before Week 24 was not counted.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Impaired Symbol Digit Modalities Test (SDMT)</measure>
    <time_frame>Baseline up to Week 96</time_frame>
    <description>The SDMT involves a simple substitution task using a reference key, the examinee has 90 seconds to pair specific numbers with given geometric figures. Responses are done verbally. The administration time is approximately 5 minutes. The total SDMT score for each visit ranging from 0-110 is defined as the total number of correct answers reported in the case report form (CRF), where high scores indicate better outcome. Impaired SDMT is defined as a decrease from baseline of at least 4 points at any post-baseline assessment up to the Week 96 visit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Brain Volume</measure>
    <time_frame>Baseline up to Week 96</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)</measure>
    <time_frame>From the first dose of study drug through the end of the study (up to approximately 116 weeks)</time_frame>
    <description>An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. A Serious AE is defined as any untoward medical occurrence that: results in death, is immediately life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, and/or causes a congenital anomaly/birth defect. A TEAE is an AE that starts or worsens after receiving study drug.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">549</enrollment>
  <condition>Relapsing Multiple Sclerosis (RMS)</condition>
  <arm_group>
    <arm_group_label>Ublituximab + Oral Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants were administered ublituximab 150 milligrams (mg), intravenous (IV) infusion over 4 hours (h) on Day 1 followed by 450 mg over 1 h on Days 15, 168, 336 and 504 (Week 72) along with the oral placebo once daily (QD) from Day 1 up to the last day of Week 95.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Teriflunomide + IV Placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants were administered teriflunomide 14 mg tablet, orally, QD from Day 1 up to the last day of Week 95 along with the placebo IV infusion on Days 1, 15, 168, 336 and 504 (Week 72).</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Ublituximab</intervention_name>
    <description>Administered as an IV infusion.</description>
    <arm_group_label>Ublituximab + Oral Placebo</arm_group_label>
    <other_name>TG-1101</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Teriflunomide</intervention_name>
    <description>Film-coated tablets administered orally.</description>
    <arm_group_label>Teriflunomide + IV Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oral Placebo</intervention_name>
    <description>Administered orally.</description>
    <arm_group_label>Ublituximab + Oral Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IV Placebo</intervention_name>
    <description>Administered as an IV infusion.</description>
    <arm_group_label>Teriflunomide + IV Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18-55 age&#xD;
&#xD;
          -  Diagnosis of RMS (McDonald criteria 2010)&#xD;
&#xD;
          -  Active disease&#xD;
&#xD;
          -  Expanded disability status scale (EDSS) 0-5.5 (inclusive) at screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Treatment with prior Anti-cluster of differentiate 20 (CD20) or other B cell directed&#xD;
             treatment&#xD;
&#xD;
          -  Treatment with the following therapies at any time prior to randomization:&#xD;
             alemtuzumab, natalizumab, teriflunomide, leflunomide and stem cell transplantation&#xD;
&#xD;
          -  Diagnosed with Primary Progressive MS (PPMS)&#xD;
&#xD;
          -  Pregnant or nursing&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>TG Therapeutics RMS Investigational Trial Site</name>
      <address>
        <city>Carlsbad</city>
        <state>California</state>
        <zip>92001</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TG Therapeutics RMS Investigational Trial Site</name>
      <address>
        <city>Long Beach</city>
        <state>California</state>
        <zip>90808</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TG Therapeutics RMS Investigational Trial Site</name>
      <address>
        <city>Pasadena</city>
        <state>California</state>
        <zip>91105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TG Therapeutics RMS Investigational Trial Site</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TG Therapeutics RMS Investigational Trial Site</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TG Therapeutics RMS Investigational Trial Site</name>
      <address>
        <city>Northbrook</city>
        <state>Illinois</state>
        <zip>60062</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TG Therapeutics RMS Investigational Trial Site</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TG Therapeutics RMS Investigational Trial Site</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TG Therapeutics RMS Investigational Trial Site</name>
      <address>
        <city>Amherst</city>
        <state>New York</state>
        <zip>14226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TG Therapeutics RMS Investigational Trial Site</name>
      <address>
        <city>Westerville</city>
        <state>Ohio</state>
        <zip>43081</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TG Therapeutics RMS Investigational Trial Site</name>
      <address>
        <city>Franklin</city>
        <state>Tennessee</state>
        <zip>37064</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TG Therapeutics RMS Investigational Trial Site</name>
      <address>
        <city>Knoxville</city>
        <state>Tennessee</state>
        <zip>37922</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TG Therapeutics RMS Investigational Trial Site</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TG Therapeutics RMS Investigational Site</name>
      <address>
        <city>Round Rock</city>
        <state>Texas</state>
        <zip>78681</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>September 7, 2017</study_first_submitted>
  <study_first_submitted_qc>September 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 11, 2017</study_first_posted>
  <results_first_submitted>November 5, 2021</results_first_submitted>
  <results_first_submitted_qc>November 5, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">December 6, 2021</results_first_posted>
  <disposition_first_submitted>May 11, 2021</disposition_first_submitted>
  <disposition_first_submitted_qc>May 11, 2021</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">May 20, 2021</disposition_first_posted>
  <last_update_submitted>November 5, 2021</last_update_submitted>
  <last_update_submitted_qc>November 5, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 6, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Sclerosis</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Teriflunomide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Data will be shared after study completion via publication.</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>September 4, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/61/NCT03277261/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 4, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/61/NCT03277261/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>A total of 549 participants were enrolled across investigative sites in Belarus, Spain, the United Kingdom, Georgia, Poland, Russia, Serbia, Ukraine, and the United States from 19 September 2017 to 6 November 2020.</recruitment_details>
      <pre_assignment_details>A total of 646 participants were screened and of those, 549 were enrolled and randomized to receive either ublituximab/oral placebo or teriflunomide/IV placebo.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Ublituximab + Oral Placebo</title>
          <description>Participants were administered ublituximab 150 milligrams (mg), intravenous (IV) infusion over 4 hours (h) on Day 1 followed by 450 mg over 1 h on Days 15, 168, 336 and 504 (Week 72) along with the oral placebo once daily (QD) from Day 1 up to the last day of Week 95.</description>
        </group>
        <group group_id="P2">
          <title>Teriflunomide + IV Placebo</title>
          <description>Participants were administered teriflunomide 14 mg tablet, orally, QD from Day 1 up to the last day of Week 95 along with the placebo IV infusion on Days 1, 15, 168, 336 and 504 (Week 72).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="274"/>
                <participants group_id="P2" count="275"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="240"/>
                <participants group_id="P2" count="252"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="34"/>
                <participants group_id="P2" count="23"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Participant Withdrawal of Consent</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Investigator / Sponsor Decision</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Pregnancy</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other-Alternative Treatment/Unspecified Reasons</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Intention-to-Treat (ITT) population consisted of all randomized participants.</population>
      <group_list>
        <group group_id="B1">
          <title>Ublituximab + Oral Placebo</title>
          <description>Participants were administered ublituximab 150 mg, IV infusion over 4 h on Day 1 followed by 450 mg over 1 h on Days 15, 168, 336 and 504 (Week 72) along with the oral placebo QD from Day 1 up to the last day of Week 95.</description>
        </group>
        <group group_id="B2">
          <title>Teriflunomide + IV Placebo</title>
          <description>Participants were administered teriflunomide 14 mg tablet, orally, QD from Day 1 up to the last day of Week 95 along with the placebo IV infusion on Days 1, 15, 168, 336 and 504 (Week 72).</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="274"/>
            <count group_id="B2" value="275"/>
            <count group_id="B3" value="549"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="36.3" spread="8.48"/>
                    <measurement group_id="B2" value="37.0" spread="9.62"/>
                    <measurement group_id="B3" value="36.7" spread="9.07"/>
                  </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="167"/>
                    <measurement group_id="B2" value="180"/>
                    <measurement group_id="B3" value="347"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="107"/>
                    <measurement group_id="B2" value="95"/>
                    <measurement group_id="B3" value="202"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="263"/>
                    <measurement group_id="B2" value="267"/>
                    <measurement group_id="B3" value="530"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Race</title>
              <category_list>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="267"/>
                    <measurement group_id="B2" value="267"/>
                    <measurement group_id="B3" value="534"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Annualized Relapse Rate (ARR)</title>
        <description>ARR is defined as the number of Independent Relapse Adjudication Panel (IRAP)-confirmed relapses per participant year. The estimate of ARR for a treatment group is the total number of relapses for participants in the respective treatment group divided by the sum of treatment duration for participants in that specific treatment group.</description>
        <time_frame>Up to 96 weeks</time_frame>
        <population>Modified Intention-to-Treat (mITT) population consisted of all participants in the ITT population who received at least one dose of study medication and have at least one baseline and post baseline efficacy assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Ublituximab + Oral Placebo</title>
            <description>Participants were administered ublituximab 150 mg, IV infusion over 4 h on Day 1 followed by 450 mg over 1 h on Days 15, 168, 336 and 504 (Week 72) along with the oral placebo QD from Day 1 up to the last day of Week 95.</description>
          </group>
          <group group_id="O2">
            <title>Teriflunomide + IV Placebo</title>
            <description>Participants were administered teriflunomide 14 mg tablet, orally, QD from Day 1 up to the last day of Week 95 along with the placebo IV infusion on Days 1, 15, 168, 336 and 504 (Week 72).</description>
          </group>
        </group_list>
        <measure>
          <title>Annualized Relapse Rate (ARR)</title>
          <description>ARR is defined as the number of Independent Relapse Adjudication Panel (IRAP)-confirmed relapses per participant year. The estimate of ARR for a treatment group is the total number of relapses for participants in the respective treatment group divided by the sum of treatment duration for participants in that specific treatment group.</description>
          <population>Modified Intention-to-Treat (mITT) population consisted of all participants in the ITT population who received at least one dose of study medication and have at least one baseline and post baseline efficacy assessment.</population>
          <units>relapses per participant-years</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="271"/>
                <count group_id="O2" value="274"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.076" lower_limit="0.042" upper_limit="0.138"/>
                    <measurement group_id="O2" value="0.188" lower_limit="0.124" upper_limit="0.283"/>
                  </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</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>GEE (Generalized Estimating Equation) model for the relapse count per participant with logarithmic link function, treatment, region, and baseline Expanded Disability Status Scale (EDSS) strata as covariates and log (years of treatment) as offset.</p_value_desc>
            <method>Negative Binomial Model</method>
            <param_type>Rate Ratio (Ublituximab/Teriflunomide)</param_type>
            <param_value>0.406</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.268</ci_lower_limit>
            <ci_upper_limit>0.615</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Number of Gadolinium (Gd)-Enhancing T1-Lesions Per Magnetic Resonance Imaging (MRI) Scan Per Participant</title>
        <description>The total number of Gd-enhancing T1-lesions were calculated as the sum of the individual number of lesions at Weeks 12, 24, 48, and 96, divided by the total number of MRI scans of the brain.</description>
        <time_frame>Weeks 12, 24, 48, and 96</time_frame>
        <population>mITT- magnetic resonance imaging (MRI) population included participants in mITT population who have baseline and post-baseline MRI efficacy assessments. Overall number of participants analyzed signifies participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Ublituximab + Oral Placebo</title>
            <description>Participants were administered ublituximab 150 mg, IV infusion over 4 h on Day 1 followed by 450 mg over 1 h on Days 15, 168, 336 and 504 (Week 72) along with the oral placebo QD from Day 1 up to the last day of Week 95.</description>
          </group>
          <group group_id="O2">
            <title>Teriflunomide + IV Placebo</title>
            <description>Participants were administered teriflunomide 14 mg tablet, orally, QD from Day 1 up to the last day of Week 95 along with the placebo IV infusion on Days 1, 15, 168, 336 and 504 (Week 72).</description>
          </group>
        </group_list>
        <measure>
          <title>Total Number of Gadolinium (Gd)-Enhancing T1-Lesions Per Magnetic Resonance Imaging (MRI) Scan Per Participant</title>
          <description>The total number of Gd-enhancing T1-lesions were calculated as the sum of the individual number of lesions at Weeks 12, 24, 48, and 96, divided by the total number of MRI scans of the brain.</description>
          <population>mITT- magnetic resonance imaging (MRI) population included participants in mITT population who have baseline and post-baseline MRI efficacy assessments. Overall number of participants analyzed signifies participants who were evaluable for this outcome measure.</population>
          <units>lesions per scan per participant</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="264"/>
                <count group_id="O2" value="269"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.016" lower_limit="0.008" upper_limit="0.032"/>
                    <measurement group_id="O2" value="0.491" lower_limit="0.355" upper_limit="0.679"/>
                  </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</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>GEE model for the relapse count per participant with logarithmic link function, treatment, region, and baseline EDSS strata as covariates and log (years of treatment) as offset.</p_value_desc>
            <method>Negative Binomial Model</method>
            <param_type>Rate Ratio (Ublituximab/Teriflunomide)</param_type>
            <param_value>0.033</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.019</ci_lower_limit>
            <ci_upper_limit>0.058</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Number of New and Enlarging T2 Hyperintense Lesions (NELs) Per MRI Scan Per Participant</title>
        <description>The total number of NELs were calculated as the sum of the individual number of lesions at Weeks 24, 48, and 96, divided by the total number of MRI scans of the brain.</description>
        <time_frame>Weeks 24, 48, and 96</time_frame>
        <population>mITT- MRI population included participants in mITT population who have baseline and post-baseline MRI efficacy assessments. Overall number of participants analyzed signifies participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Ublituximab + Oral Placebo</title>
            <description>Participants were administered ublituximab 150 mg, IV infusion over 4 h on Day 1 followed by 450 mg over 1 h on Days 15, 168, 336 and 504 (Week 72) along with the oral placebo QD from Day 1 up to the last day of Week 95.</description>
          </group>
          <group group_id="O2">
            <title>Teriflunomide + IV Placebo</title>
            <description>Participants were administered teriflunomide 14 mg tablet, orally, QD from Day 1 up to the last day of Week 95 along with the placebo IV infusion on Days 1, 15, 168, 336 and 504 (Week 72).</description>
          </group>
        </group_list>
        <measure>
          <title>Total Number of New and Enlarging T2 Hyperintense Lesions (NELs) Per MRI Scan Per Participant</title>
          <description>The total number of NELs were calculated as the sum of the individual number of lesions at Weeks 24, 48, and 96, divided by the total number of MRI scans of the brain.</description>
          <population>mITT- MRI population included participants in mITT population who have baseline and post-baseline MRI efficacy assessments. Overall number of participants analyzed signifies participants who were evaluable for this outcome measure.</population>
          <units>lesions per scan per participant</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="260"/>
                <count group_id="O2" value="267"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.213" lower_limit="0.144" upper_limit="0.316"/>
                    <measurement group_id="O2" value="2.789" lower_limit="2.136" upper_limit="3.643"/>
                  </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</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>GEE model for the relapse count per participant with logarithmic link function, treatment, region, and baseline EDSS strata as covariates and log (years of treatment) as offset.</p_value_desc>
            <method>Negative Binomial Model</method>
            <param_type>Rate Ratio (Ublituximab/Teriflunomide)</param_type>
            <param_value>0.076</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.056</ci_lower_limit>
            <ci_upper_limit>0.104</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Confirmed Disability Progression (CDP) for at Least 12 Weeks</title>
        <description>12-week CDP is defined as an increase in EDSS at least 1 point higher than the baseline EDSS if the baseline EDSS is ≤5.5 or at least 0.5 higher than the baseline EDSS if the baseline EDSS is &gt;5.5. The EDSS is based on a standard neurological examination, (pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, and cerebral) and ambulation function system assessments. The EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death) where higher scores indicate disability. The time to onset of 12-week CDP is the time to progression to the EDSS change defined above.</description>
        <time_frame>Up to Week 96</time_frame>
        <population>mITT population consisted of all participants in the ITT population who received at least one dose of study medication and have at least one baseline and post baseline efficacy assessment. As per protocol, data was summarized for the mITT Population using pooled data from participants in this study and TG1101-RMS302 [NCT03277248].</population>
        <group_list>
          <group group_id="O1">
            <title>Ublituximab + Oral Placebo</title>
            <description>Participants were administered ublituximab 150 mg, IV infusion over 4 h on Day 1 followed by 450 mg over 1 h on Days 15, 168, 336 and 504 (Week 72) along with the oral placebo QD from Day 1 up to the last day of Week 95.</description>
          </group>
          <group group_id="O2">
            <title>Teriflunomide + IV Placebo</title>
            <description>Participants were administered teriflunomide 14 mg tablet, orally, QD from Day 1 up to the last day of Week 95 along with the placebo IV infusion on Days 1, 15, 168, 336 and 504 (Week 72).</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Confirmed Disability Progression (CDP) for at Least 12 Weeks</title>
          <description>12-week CDP is defined as an increase in EDSS at least 1 point higher than the baseline EDSS if the baseline EDSS is ≤5.5 or at least 0.5 higher than the baseline EDSS if the baseline EDSS is &gt;5.5. The EDSS is based on a standard neurological examination, (pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, and cerebral) and ambulation function system assessments. The EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death) where higher scores indicate disability. The time to onset of 12-week CDP is the time to progression to the EDSS change defined above.</description>
          <population>mITT population consisted of all participants in the ITT population who received at least one dose of study medication and have at least one baseline and post baseline efficacy assessment. As per protocol, data was summarized for the mITT Population using pooled data from participants in this study and TG1101-RMS302 [NCT03277248].</population>
          <units>weeks</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="543"/>
                <count group_id="O2" value="546"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">Median and Inter Quartile Range was not reached due to the low number of participants with events.</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="NA" upper_limit="NA">Median and Inter Quartile Range was not reached due to the low number of participants with events.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With No Evidence of Disease Activity (NEDA)</title>
        <description>A participant with NEDA is defined as a participant without relapses confirmed by the IRAP, without MRI activities (no T1 Gd+ lesions and no new/enlarging T2 lesions), and no 12-week CDP. Any evidence of disease activity from Week 24 to Week 96 was counted as not reaching NEDA. Any evidence of disease activity before Week 24 was not counted.</description>
        <time_frame>Week 24 up to Week 96</time_frame>
        <population>mITT population consisted of all participants in the ITT population who received at least one dose of study medication and have at least one baseline and post baseline efficacy assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Ublituximab + Oral Placebo</title>
            <description>Participants were administered ublituximab 150 mg, IV infusion over 4 h on Day 1 followed by 450 mg over 1 h on Days 15, 168, 336 and 504 (Week 72) along with the oral placebo QD from Day 1 up to the last day of Week 95.</description>
          </group>
          <group group_id="O2">
            <title>Teriflunomide + IV Placebo</title>
            <description>Participants were administered teriflunomide 14 mg tablet, orally, QD from Day 1 up to the last day of Week 95 along with the placebo IV infusion on Days 1, 15, 168, 336 and 504 (Week 72).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With No Evidence of Disease Activity (NEDA)</title>
          <description>A participant with NEDA is defined as a participant without relapses confirmed by the IRAP, without MRI activities (no T1 Gd+ lesions and no new/enlarging T2 lesions), and no 12-week CDP. Any evidence of disease activity from Week 24 to Week 96 was counted as not reaching NEDA. Any evidence of disease activity before Week 24 was not counted.</description>
          <population>mITT population consisted of all participants in the ITT population who received at least one dose of study medication and have at least one baseline and post baseline efficacy assessment.</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="271"/>
                <count group_id="O2" value="274"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.6"/>
                    <measurement group_id="O2" value="15.0"/>
                  </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</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Logistic regression model with treatment, region, baseline EDSS strata and log transformed baseline MRI lesion counts (T1 unenhancing, T2, Gd enhancing) as covariates.</p_value_desc>
            <method>Regression, Logistic</method>
            <param_type>Odds Ratio (Ublituximab/Teriflunomide)</param_type>
            <param_value>5.442</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>3.536</ci_lower_limit>
            <ci_upper_limit>8.375</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Impaired Symbol Digit Modalities Test (SDMT)</title>
        <description>The SDMT involves a simple substitution task using a reference key, the examinee has 90 seconds to pair specific numbers with given geometric figures. Responses are done verbally. The administration time is approximately 5 minutes. The total SDMT score for each visit ranging from 0-110 is defined as the total number of correct answers reported in the case report form (CRF), where high scores indicate better outcome. Impaired SDMT is defined as a decrease from baseline of at least 4 points at any post-baseline assessment up to the Week 96 visit.</description>
        <time_frame>Baseline up to Week 96</time_frame>
        <population>mITT population consisted of all participants in the ITT population who received at least one dose of study medication and have at least one baseline and post baseline efficacy assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Ublituximab + Oral Placebo</title>
            <description>Participants were administered ublituximab 150 mg, IV infusion over 4 h on Day 1 followed by 450 mg over 1 h on Days 15, 168, 336 and 504 (Week 72) along with the oral placebo QD from Day 1 up to the last day of Week 95.</description>
          </group>
          <group group_id="O2">
            <title>Teriflunomide + IV Placebo</title>
            <description>Participants were administered Teriflunomide 14 mg tablet, orally, QD from Day 1 up to the last day of Week 95 along with the placebo IV infusion on Days 1, 15, 168, 336 and 504 (Week 72).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Impaired Symbol Digit Modalities Test (SDMT)</title>
          <description>The SDMT involves a simple substitution task using a reference key, the examinee has 90 seconds to pair specific numbers with given geometric figures. Responses are done verbally. The administration time is approximately 5 minutes. The total SDMT score for each visit ranging from 0-110 is defined as the total number of correct answers reported in the case report form (CRF), where high scores indicate better outcome. Impaired SDMT is defined as a decrease from baseline of at least 4 points at any post-baseline assessment up to the Week 96 visit.</description>
          <population>mITT population consisted of all participants in the ITT population who received at least one dose of study medication and have at least one baseline and post baseline efficacy assessment.</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="271"/>
                <count group_id="O2" value="274"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.2"/>
                    <measurement group_id="O2" value="31.8"/>
                  </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</non_inferiority_type>
            <p_value>=0.4669</p_value>
            <p_value_desc>Logistic regression model with treatment, region, baseline EDSS strata, and log-transformed baseline MRI counts (T1 unenhancing, T2, Gd enhancing) as covariates.</p_value_desc>
            <method>Logistic Regression</method>
            <param_type>Odds Ratio (Ublituximab/Teriflunomide)</param_type>
            <param_value>0.872</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.603</ci_lower_limit>
            <ci_upper_limit>1.261</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Brain Volume</title>
        <time_frame>Baseline up to Week 96</time_frame>
        <population>mITT- MRI population included participants in mITT population who have baseline and post-baseline MRI efficacy assessments. Overall number of participants analyzed signifies participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Ublituximab + Oral Placebo</title>
            <description>Participants were administered ublituximab 150 mg, IV infusion over 4 h on Day 1 followed by 450 mg over 1 h on Days 15, 168, 336 and 504 (Week 72) along with the oral placebo QD from Day 1 up to the last day of Week 95.</description>
          </group>
          <group group_id="O2">
            <title>Teriflunomide + IV Placebo</title>
            <description>Participants were administered teriflunomide 14 mg tablet, orally, QD from Day 1 up to the last day of Week 95 along with the placebo IV infusion on Days 1, 15, 168, 336 and 504 (Week 72).</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Brain Volume</title>
          <population>mITT- MRI population included participants in mITT population who have baseline and post-baseline MRI efficacy assessments. Overall number of participants analyzed signifies participants who were evaluable for this outcome measure.</population>
          <units>percent change</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="204"/>
                <count group_id="O2" value="207"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.197" lower_limit="-0.228" upper_limit="-0.166"/>
                    <measurement group_id="O2" value="-0.125" lower_limit="-0.155" upper_limit="-0.095"/>
                  </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</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>The model includes treatment, region, baseline EDSS strata, visit, treatment-by-visit interaction, and baseline volume (cube root transformed) as covariates and an unstructured covariance matrix.</p_value_desc>
            <method>Mixed Model Repeated Measures (MMRM)</method>
            <param_type>Least squares mean difference</param_type>
            <param_value>-0.072</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.107</ci_lower_limit>
            <ci_upper_limit>-0.036</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)</title>
        <description>An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. A Serious AE is defined as any untoward medical occurrence that: results in death, is immediately life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, and/or causes a congenital anomaly/birth defect. A TEAE is an AE that starts or worsens after receiving study drug.</description>
        <time_frame>From the first dose of study drug through the end of the study (up to approximately 116 weeks)</time_frame>
        <population>Safety population included all participants who received at least one dose of study drug (ublituximab or teriflunomide, with corresponding placebos).</population>
        <group_list>
          <group group_id="O1">
            <title>Ublituximab + Oral Placebo</title>
            <description>Participants were administered ublituximab 150 mg, IV infusion over 4 h on Day 1 followed by 450 mg over 1 h on Days 15, 168, 336 and 504 (Week 72) along with the oral placebo QD from Day 1 up to the last day of Week 95.</description>
          </group>
          <group group_id="O2">
            <title>Teriflunomide + IV Placebo</title>
            <description>Participants were administered teriflunomide 14 mg tablet, orally, QD from Day 1 up to the last day of Week 95 along with the placebo IV infusion on Days 1, 15, 168, 336 and 504 (Week 72).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)</title>
          <description>An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. A Serious AE is defined as any untoward medical occurrence that: results in death, is immediately life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, and/or causes a congenital anomaly/birth defect. A TEAE is an AE that starts or worsens after receiving study drug.</description>
          <population>Safety population included all participants who received at least one dose of study drug (ublituximab or teriflunomide, with corresponding placebos).</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="273"/>
                <count group_id="O2" value="275"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="86.1"/>
                    <measurement group_id="O2" value="89.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TESAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.4"/>
                    <measurement group_id="O2" value="6.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From the first dose of study drug through the end of the study (up to approximately 116 weeks)</time_frame>
      <desc>All-Cause Mortality: All the enrolled participants; Adverse Events: Safety population included all participants who received at least one dose of study drug (ublituximab or teriflunomide, with corresponding placebos).</desc>
      <group_list>
        <group group_id="E1">
          <title>Ublituximab + Oral Placebo</title>
          <description>Participants were administered ublituximab 150 mg, IV infusion over 4 h on Day 1 followed by 450 mg over 1 h on Days 15, 168, 336 and 504 (Week 72) along with the oral placebo QD from Day 1 up to the last day of Week 95.</description>
        </group>
        <group group_id="E2">
          <title>Teriflunomide + IV Placebo</title>
          <description>Participants were administered teriflunomide 14 mg tablet, orally, QD from Day 1 up to the last day of Week 95 along with the placebo IV infusion on Days 1, 15, 168, 336 and 504 (Week 72).</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (23.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="274"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="31" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="275"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="275"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperthyroidism</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="275"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pancreatitis chronic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Oesophageal achalasia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="275"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="275"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaphylactic reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Hypersensitivity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="275"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>COVID-19 pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Central nervous system enteroviral infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Appendicitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Bullous erysipelas</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Encephalitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Measles</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Meningoencephalitis viral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Peritonsillar abscess</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Pulmonary tuberculosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Salpingitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Bacterial infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Lyme disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Pyelonephritis acute</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="275"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Concussion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Femoral neck fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Patella fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="275"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="275"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Intervertebral disc disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="275"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Neurological symptom</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Acoustic neuritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="275"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Pregnancy, puerperium and perinatal conditions</title>
            <event_list>
              <event>
                <sub_title>Ectopic pregnancy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="275"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Affective disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Mental disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Psychotic disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="275"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Tubulointerstitial nephritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="275"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Ovarian cyst ruptured</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Uterine haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="275"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Angioedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Rosacea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="275"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Medical device removal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="275"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Varicose vein</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="275"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (23.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="197" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="181" subjects_at_risk="275"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Lymphopenia</sub_title>
                <counts group_id="E1" subjects_affected="27" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="275"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="29" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="26" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="275"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="41" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="275"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="34" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="44" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection viral</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="275"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="33" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="275"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="30" subjects_at_risk="275"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="275"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="84" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="59" subjects_at_risk="275"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="36" subjects_at_risk="275"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="273"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="275"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>TG Therapeutics Clinical Support Team</name_or_title>
      <organization>TG Therapeutics</organization>
      <phone>1-877-575-8489</phone>
      <email>clinicalsupport@tgtxinc.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/NCT03277261
org study id: TG1101-RMS301
secondary id: 2017-000638-75
nct id: NCT03277261
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study determines the Annualized Relapse Rate (ARR) in participants with RMS after 96
      weeks (approximately 2 years) treatment with intravenous (IV) infusion of ublituximab/oral
      placebo compared to 14 mg oral teriflunomide/IV placebo.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized, multi-center, double-blinded, active-controlled study
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Double-blinded, active-controlled study
measure: Annualized Relapse Rate (ARR)
time frame: Up to 96 weeks
description: ARR is defined as the number of Independent Relapse Adjudication Panel (IRAP)-confirmed relapses per participant year. The estimate of ARR for a treatment group is the total number of relapses for participants in the respective treatment group divided by the sum of treatment duration for participants in that specific treatment group.
measure: Total Number of Gadolinium (Gd)-Enhancing T1-Lesions Per Magnetic Resonance Imaging (MRI) Scan Per Participant
time frame: Weeks 12, 24, 48, and 96
description: The total number of Gd-enhancing T1-lesions were calculated as the sum of the individual number of lesions at Weeks 12, 24, 48, and 96, divided by the total number of MRI scans of the brain.
measure: Total Number of New and Enlarging T2 Hyperintense Lesions (NELs) Per MRI Scan Per Participant
time frame: Weeks 24, 48, and 96
description: The total number of NELs were calculated as the sum of the individual number of lesions at Weeks 24, 48, and 96, divided by the total number of MRI scans of the brain.
measure: Time to Confirmed Disability Progression (CDP) for at Least 12 Weeks
time frame: Up to Week 96
description: 12-week CDP is defined as an increase in EDSS at least 1 point higher than the baseline EDSS if the baseline EDSS is ≤5.5 or at least 0.5 higher than the baseline EDSS if the baseline EDSS is >5.5. The EDSS is based on a standard neurological examination, (pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, and cerebral) and ambulation function system assessments. The EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death) where higher scores indicate disability. The time to onset of 12-week CDP is the time to progression to the EDSS change defined above.
measure: Percentage of Participants With No Evidence of Disease Activity (NEDA)
time frame: Week 24 up to Week 96
description: A participant with NEDA is defined as a participant without relapses confirmed by the IRAP, without MRI activities (no T1 Gd+ lesions and no new/enlarging T2 lesions), and no 12-week CDP. Any evidence of disease activity from Week 24 to Week 96 was counted as not reaching NEDA. Any evidence of disease activity before Week 24 was not counted.
measure: Percentage of Participants With Impaired Symbol Digit Modalities Test (SDMT)
time frame: Baseline up to Week 96
description: The SDMT involves a simple substitution task using a reference key, the examinee has 90 seconds to pair specific numbers with given geometric figures. Responses are done verbally. The administration time is approximately 5 minutes. The total SDMT score for each visit ranging from 0-110 is defined as the total number of correct answers reported in the case report form (CRF), where high scores indicate better outcome. Impaired SDMT is defined as a decrease from baseline of at least 4 points at any post-baseline assessment up to the Week 96 visit.
measure: Percent Change From Baseline in Brain Volume
time frame: Baseline up to Week 96
measure: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
time frame: From the first dose of study drug through the end of the study (up to approximately 116 weeks)
description: An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. A Serious AE is defined as any untoward medical occurrence that: results in death, is immediately life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, and/or causes a congenital anomaly/birth defect. A TEAE is an AE that starts or worsens after receiving study drug.
arm group label: Ublituximab + Oral Placebo
arm group type: Experimental
description: Participants were administered ublituximab 150 milligrams (mg), intravenous (IV) infusion over 4 hours (h) on Day 1 followed by 450 mg over 1 h on Days 15, 168, 336 and 504 (Week 72) along with the oral placebo once daily (QD) from Day 1 up to the last day of Week 95.
arm group label: Teriflunomide + IV Placebo
arm group type: Active Comparator
description: Participants were administered teriflunomide 14 mg tablet, orally, QD from Day 1 up to the last day of Week 95 along with the placebo IV infusion on Days 1, 15, 168, 336 and 504 (Week 72).
intervention type: Biological
intervention name: Ublituximab
description: Administered as an IV infusion.
arm group label: Ublituximab + Oral Placebo
other name: TG-1101
intervention type: Drug
intervention name: Teriflunomide
description: Film-coated tablets administered orally.
arm group label: Teriflunomide + IV Placebo
intervention type: Drug
intervention name: Oral Placebo
description: Administered orally.
arm group label: Ublituximab + Oral Placebo
intervention type: Drug
intervention name: IV Placebo
description: Administered as an IV infusion.
arm group label: Teriflunomide + IV Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: No
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country: United States
responsible party type: Sponsor
mesh term: Multiple Sclerosis
mesh term: Sclerosis
mesh term: Teriflunomide
sharing ipd: Undecided
ipd description: Data will be shared after study completion via publication.
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 