<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/NCT02215616</url>
  </required_header>
  <id_info>
    <org_study_id>TV5600-CNS-20007</org_study_id>
    <secondary_id>2014-000418-75</secondary_id>
    <nct_id>NCT02215616</nct_id>
  </id_info>
  <brief_title>A Clinical Study in Participants With Huntington's Disease (HD) to Assess Efficacy and Safety of Three Oral Doses of Laquinimod</brief_title>
  <acronym>LEGATO-HD</acronym>
  <official_title>A Multicenter, Multinational, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Laquinimod (0.5, 1.0 and 1.5 mg/Day) as Treatment in Patients With Huntington's Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Teva Branded Pharmaceutical Products R&amp;D, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Teva Branded Pharmaceutical Products R&amp;D, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to assess the efficacy of laquinimod as treatment in&#xD;
      participants with HD after 52 weeks using the Unified Huntington's Disease Rating Scale Total&#xD;
      Motor Score (UHDRS-TMS or TMS).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 28, 2014</start_date>
  <completion_date type="Actual">June 19, 2018</completion_date>
  <primary_completion_date type="Actual">June 19, 2018</primary_completion_date>
  <phase>Phase 2</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in UHDRS-TMS at Week 52</measure>
    <time_frame>Baseline, Week 52</time_frame>
    <description>UHDRS is a research tool developed by Huntington Disease (HD) Study Group to provide a uniform assessment of the clinical features and course of HD. Components of the full UHDRS assess motor function, cognition, behaviour, functional abilities, independence scale and total functional capacities. Motor function assessment includes TMS and Total Functional Capacity (TFC) score. The UHDRS TMS assesses all the motor features of HD and includes maximal chorea, maximal dystonia, ocular pursuit, saccade initiation and velocity, dysarthria, tongue protrusion, finger tapping, hand pronation and supination, luria, rigidity, bradykinesia, gait, tandem walking, and retropulsion pull test. Each of these was rated on a scale of 0 (normal motor function) to 4 (severely impaired motor function). TMS score is a sum of individual scores ranging from 0 (normal motor function) to 124 (severely impaired motor function). Lower TMS scores indicate better motor function.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Caudate Volume (Brain Atrophy) at Week 52</measure>
    <time_frame>Baseline, Week 52</time_frame>
    <description>Brain atrophy was assessed using magnetic resonance imaging (MRI) measures of caudate volume. Caudate volume atrophy is a sensitive biomarker in very early HD and correlates with disease progression. Brain atrophy in the caudate refers to the shrinkage in volume, so that a decrease in volume is a positive value, while an increase in volume is a negative value. Percent change in caudate volume at Week 52 was calculated as the change in caudate volume since the baseline visit, divided by the baseline caudate volume and multiplied by 100.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">352</enrollment>
  <condition>Huntington's Disease</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive 3 capsules of matching laquinimod placebo, orally once daily for 52 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Laquinimod 0.5 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive 1 capsule of laquinimod 0.5 milligrams (mg) and 2 capsules of matching placebo, orally once daily for 52 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Laquinimod 1.0 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive 2 capsule of laquinimod 0.5 mg (total 1.0 mg laquinimod) and 1 capsule of matching placebo, orally once daily for 52 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Laquinimod 1.5 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive 3 capsules of laquinimod 0.5 mg (total 1.5 mg laquinimod), orally once daily.&#xD;
Note: The treatment of this high dose arm was discontinued as of 10 January 2016.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Laquinimod</intervention_name>
    <description>Laquinimod capsules will be administered as per the dose and schedule specified in the respective arms.</description>
    <arm_group_label>Laquinimod 0.5 mg</arm_group_label>
    <arm_group_label>Laquinimod 1.0 mg</arm_group_label>
    <arm_group_label>Laquinimod 1.5 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Matching laquinimod placebo will be administered as per the schedule specified in the respective arms.</description>
    <arm_group_label>Laquinimod 0.5 mg</arm_group_label>
    <arm_group_label>Laquinimod 1.0 mg</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Documentation of prior positive genetic testing for HD, or a clinical diagnosis of&#xD;
             symptomatic HD.&#xD;
&#xD;
          -  Presence of 36-49 cytosine-adenosine-guanine (CAG) repeats, inclusive, in the&#xD;
             huntingtin gene based on centralized CAG testing during screening.&#xD;
&#xD;
          -  Male or female between 21-55 years of age, inclusive, with an onset of HD at or after&#xD;
             18 years of age.&#xD;
&#xD;
          -  Women of child-bearing potential (women who are not post menopausal or who have&#xD;
             undergone surgical sterilization) must practice an acceptable method of birth control&#xD;
             for 30 days before taking the study treatment, and 2 acceptable methods of birth&#xD;
             control during all study duration and until 30 days after the last dose of treatment&#xD;
             was administered.&#xD;
&#xD;
          -  A sum of greater than (&gt;) 5 points on the UHDRS-TMS at the screening visit.&#xD;
&#xD;
          -  Able and willing to provide written informed consent prior to any study related&#xD;
             procedure being performed at the screening visit. Participants with a legal guardian&#xD;
             should be consented according to local requirements.&#xD;
&#xD;
          -  Willing to provide a blood sample for genomic CAG analysis at the screening visit.&#xD;
&#xD;
          -  Willing and able to take oral medication and able to comply with the study specific&#xD;
             procedures.&#xD;
&#xD;
          -  Ambulatory, being able to travel to the study center, and judged by the investigator&#xD;
             as likely to be able to continue to travel for the duration of the study.&#xD;
&#xD;
          -  Availability and willingness of a caregiver, informant, or family member to provide&#xD;
             input at study visits assessing Clinician's Interview-Based Impression of Change&#xD;
             (CIBIC)-Plus, Clinical Dementia Rating - Sum of Boxes (CDR-SB), Problem Behaviors&#xD;
             Assessment-Short form (PBA-s) and Huntington's Disease Quality of Life (HD-QoL). A&#xD;
             caregiver is recommended to be someone who attends to the participant at least 2 to 3&#xD;
             times per week for at least 3 hours per occasion, and the suitability of the caregiver&#xD;
             should be judged by the investigator.&#xD;
&#xD;
          -  For participants taking allowed antidepressant medication, the dosing of medication&#xD;
             must have been kept constant for at least 30 days before baseline and must be kept&#xD;
             constant during the study.&#xD;
&#xD;
               -  Additional criteria may apply, please contact the investigator for more&#xD;
                  information.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Use of immunosuppressive agents, or cytotoxic agents, including cyclophosphamide and&#xD;
             azatioprine within 12 months prior to screening.&#xD;
&#xD;
          -  Previous use of laquinimod.&#xD;
&#xD;
          -  Use of moderate/strong inhibitors of cytochrome P450 (CYP)3A4 within 2 weeks prior to&#xD;
             randomization.&#xD;
&#xD;
          -  Use of inducers of CYP3A4 within 2 weeks prior to randomization.&#xD;
&#xD;
          -  Pregnant or breastfeeding.&#xD;
&#xD;
          -  Participants with a clinically significant or unstable medical or surgical condition&#xD;
             that may put the participant at risk when participating in the study or may influence&#xD;
             the results of the study or affect the participant's ability to take part in the&#xD;
             study, as determined by medical history, physical examinations, electrocardiogram&#xD;
             (ECG), or laboratory tests. Such conditions may include:&#xD;
&#xD;
               -  A major cardiovascular event (for example; myocardial infarction, acute coronary&#xD;
                  syndrome, de-compensated congestive heart failure, pulmonary embolism, coronary&#xD;
                  revascularization) that occurred prior to randomization.&#xD;
&#xD;
               -  Any acute pulmonary disorder.&#xD;
&#xD;
               -  A central nervous system (CNS) disorder other than HD that may jeopardize the&#xD;
                  participant's participation in the study, including such disorders that are&#xD;
                  demonstrated on the baseline MRI (based on local read).&#xD;
&#xD;
               -  A gastrointestinal disorder that may affect the absorption of study medication.&#xD;
&#xD;
               -  Acute or chronic renal disease including acute kidney injury (AKI).&#xD;
&#xD;
               -  Any form of acute or chronic liver disease.&#xD;
&#xD;
               -  Known human immunodeficiency virus (HIV) positive status. Participants will&#xD;
                  undergo an HIV test at screening per local requirements, if applicable.&#xD;
&#xD;
               -  Any malignancies, excluding basal cell carcinoma, in the 5 years prior to&#xD;
                  randomization.&#xD;
&#xD;
          -  Any clinically significant, abnormal, screening laboratory result which in the opinion&#xD;
             of the investigator, affects the participant' suitability for the study or puts the&#xD;
             participant at risk if he/she enters the study.&#xD;
&#xD;
          -  Unsuitable for MRI (for example; claustrophobia, metal implants).&#xD;
&#xD;
          -  Alcohol and/or drug abuse within the 12 months prior to screening, as defined by&#xD;
             Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition Text Revision&#xD;
             (DSM IV TR) criteria for substance abuse.&#xD;
&#xD;
          -  Participants with active suicidal ideation during the past month as measured by a most&#xD;
             severe suicide ideation score of 4 (Active Suicidal Ideation with Some Intent to Act,&#xD;
             without Specific Plan) or 5 (Active Suicidal Ideation with Specific Plan and Intent)&#xD;
             on the baseline screening Columbia-Suicide Severity Rating Scale (C-SSRS) or&#xD;
             participants who answer &quot;Yes&quot; on any of the 5 C-SSRS Suicidal Behavior Items (actual&#xD;
             attempt, interrupted attempt, aborted attempt, preparatory acts, or behavior) if the&#xD;
             attempt or acts were performed within 1 year of screening, or participants who, in the&#xD;
             opinion of the investigator, present a serious risk of suicide.&#xD;
&#xD;
          -  Participants with known intracranial neoplasms, vascular malformations, or&#xD;
             intracranial hemorrhage.&#xD;
&#xD;
          -  Known drug hypersensitivity that would preclude administration of laquinimod or&#xD;
             placebo, such as hypersensitivity to mannitol, meglumine or sodium stearyl fumarate.&#xD;
&#xD;
          -  Swallowing difficulties that would preclude administration of laquinimod or placebo&#xD;
             capsules.&#xD;
&#xD;
          -  Treatment with any investigational product within 30 days of screening or participants&#xD;
             planning to participate in another clinical study assessing any investigational&#xD;
             product during the study. Participants in non-interventional and/or observational&#xD;
             studies will not be excluded from participating in this study.&#xD;
&#xD;
          -  Treatment with tetrabenazine within 30 days of the study baseline visit.&#xD;
&#xD;
          -  Treatment with antipsychotic medication within 30 days of the study baseline visit.&#xD;
&#xD;
               -  Additional criteria may apply, please contact the investigator for more&#xD;
                  information&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Teva Investigational Site 12566</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92037</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 12565</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 12567</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 12575</name>
      <address>
        <city>Englewood</city>
        <state>Colorado</state>
        <zip>80113</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 13490</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 13326</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 12568</name>
      <address>
        <city>Wichita</city>
        <state>Kansas</state>
        <zip>67226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 12574</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287-0005</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 12571</name>
      <address>
        <city>Golden Valley</city>
        <state>Minnesota</state>
        <zip>55427</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 12572</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 12570</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 12569</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14618</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 13489</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38163</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 13325</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 12815</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 12576</name>
      <address>
        <city>Kirkland</city>
        <state>Washington</state>
        <zip>98034</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 11080</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V6T 2B5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 11118</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1G 4G3</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 11079</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M3B 2S7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 11124</name>
      <address>
        <city>Edmonton</city>
        <zip>T6G 2G3</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 54108</name>
      <address>
        <city>Prague</city>
        <zip>12800</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 32480</name>
      <address>
        <city>Berlin</city>
        <zip>10117</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 32482</name>
      <address>
        <city>Bochum</city>
        <zip>44791</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 32618</name>
      <address>
        <city>Erlangen</city>
        <zip>91054</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 32483</name>
      <address>
        <city>Munchen</city>
        <zip>81675</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 32481</name>
      <address>
        <city>Munster</city>
        <zip>48149</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 32479</name>
      <address>
        <city>Ulm</city>
        <zip>89081</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 30168</name>
      <address>
        <city>Bologna</city>
        <zip>40139</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 30098</name>
      <address>
        <city>Milano</city>
        <zip>20133</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 30100</name>
      <address>
        <city>Milano</city>
        <zip>20133</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 30097</name>
      <address>
        <city>Napoli</city>
        <zip>80131</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 30099</name>
      <address>
        <city>San Giovanni Rotondo</city>
        <zip>71013</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 38066</name>
      <address>
        <city>Leiden</city>
        <zip>2333 ZA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 36026</name>
      <address>
        <city>Lisboa</city>
        <zip>1649-035</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 50379</name>
      <address>
        <city>Kazan</city>
        <zip>420101</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 50380</name>
      <address>
        <city>Moscow</city>
        <zip>125367</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 50381</name>
      <address>
        <city>Nyznij Novgorod</city>
        <zip>603126</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 31185</name>
      <address>
        <city>Barakaldo</city>
        <zip>48903</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 31097</name>
      <address>
        <city>Barcelona</city>
        <zip>8036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 31110</name>
      <address>
        <city>Barcelona</city>
        <zip>8041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 31186</name>
      <address>
        <city>Burgos</city>
        <zip>09006</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 31131</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 31187</name>
      <address>
        <city>Sevilla</city>
        <zip>41009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 34176</name>
      <address>
        <city>Aberdeen</city>
        <zip>AB25 2ZN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 34177</name>
      <address>
        <city>Birmingham</city>
        <zip>B15 2SG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 34194</name>
      <address>
        <city>Liverpool</city>
        <zip>L9 7LJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 34179</name>
      <address>
        <city>London</city>
        <zip>NW1 2PG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 34209</name>
      <address>
        <city>London</city>
        <zip>SE1 9RT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 34204</name>
      <address>
        <city>London</city>
        <zip>SW17 0QT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 34203</name>
      <address>
        <city>London</city>
        <zip>W12 0NN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 34175</name>
      <address>
        <city>Manchester</city>
        <zip>M13 9WL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 34215</name>
      <address>
        <city>Newcastle-Upon-Tyne</city>
        <zip>NE6 4QD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Teva Investigational Site 34216</name>
      <address>
        <city>Sheffield</city>
        <zip>S5 7AU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>Czechia</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Netherlands</country>
    <country>Portugal</country>
    <country>Russian Federation</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Czech Republic</country>
    <country>France</country>
    <country>India</country>
    <country>Israel</country>
  </removed_countries>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>August 12, 2014</study_first_submitted>
  <study_first_submitted_qc>August 12, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2014</study_first_posted>
  <results_first_submitted>May 29, 2019</results_first_submitted>
  <results_first_submitted_qc>May 29, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">June 19, 2019</results_first_posted>
  <last_update_submitted>April 30, 2020</last_update_submitted>
  <last_update_submitted_qc>April 30, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 4, 2020</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>Huntington Disease</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>February 16, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/16/NCT02215616/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>June 19, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/16/NCT02215616/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>A total of 468 participants were screened, of whom 116 participants were screen failures and 352 participants were enrolled. Of 352 enrolled participants, 123 participants were randomized in 1:1:1:1 ratio to receive laquinimod 0.5, 1.0, 1.5 milligrams/day (mg/day), or matching placebo prior to 10 January 2016.</recruitment_details>
      <pre_assignment_details>As of 10 January 2016; following recommendation of Data Safety Monitoring Board (DSMB), treatment of laquinimod 1.5 mg dose arm was discontinued as a proactive safety measure. After 10 January 2016; additional eligible participants, who were enrolled, were randomized in 1:1:1 ratio to receive laquinimod 0.5 mg/day, 1.0 mg/day, or matching placebo.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo</title>
          <description>Participants received 3 capsules of matching laquinimod placebo, orally once daily for 52 weeks.</description>
        </group>
        <group group_id="P2">
          <title>Laquinimod 0.5 mg</title>
          <description>Participants received 1 capsule of laquinimod 0.5 mg and 2 capsules of matching placebo, orally once daily for 52 weeks.</description>
        </group>
        <group group_id="P3">
          <title>Laquinimod 1.0 mg</title>
          <description>Participants received 2 capsules of laquinimod 0.5 mg (total 1.0 mg laquinimod) and 1 capsule of matching placebo, orally once daily for 52 weeks.</description>
        </group>
        <group group_id="P4">
          <title>Laquinimod 1.5 mg</title>
          <description>Participants received 3 capsules of laquinimod 0.5 mg (total 1.5 mg laquinimod), orally once daily. The treatment of this high dose arm was discontinued as of 10 January 2016.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="108"/>
                <participants group_id="P2" count="107"/>
                <participants group_id="P3" count="107"/>
                <participants group_id="P4" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received at Least 1 Dose of Study Drug</title>
              <participants_list>
                <participants group_id="P1" count="108"/>
                <participants group_id="P2" count="107"/>
                <participants group_id="P3" count="106"/>
                <participants group_id="P4" count="29"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="97"/>
                <participants group_id="P2" count="90"/>
                <participants group_id="P3" count="93"/>
                <participants group_id="P4" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="17"/>
                <participants group_id="P3" count="14"/>
                <participants group_id="P4" count="13"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Sponsor requested to stop study drug</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="9"/>
                <participants group_id="P4" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="8"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Non-compliance</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other than specified</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Intent-to-treat (ITT) population included all randomized participants.</population>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
          <description>Participants received 3 capsules of matching laquinimod placebo, orally once daily for 52 weeks.</description>
        </group>
        <group group_id="B2">
          <title>Laquinimod 0.5 mg</title>
          <description>Participants received 1 capsule of laquinimod 0.5 mg and 2 capsules of matching placebo, orally once daily for 52 weeks.</description>
        </group>
        <group group_id="B3">
          <title>Laquinimod 1.0 mg</title>
          <description>Participants received 2 capsules of laquinimod 0.5 mg (total 1.0 mg laquinimod) and 1 capsule of matching placebo, orally once daily for 52 weeks.</description>
        </group>
        <group group_id="B4">
          <title>Laquinimod 1.5 mg</title>
          <description>Participants received 3 capsules of laquinimod 0.5 mg (total 1.5 mg laquinimod), orally once daily. The treatment of this high dose arm was discontinued as of 10 January 2016.</description>
        </group>
        <group group_id="B5">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="108"/>
            <count group_id="B2" value="107"/>
            <count group_id="B3" value="107"/>
            <count group_id="B4" value="30"/>
            <count group_id="B5" value="352"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="108"/>
                    <count group_id="B2" value="107"/>
                    <count group_id="B3" value="107"/>
                    <count group_id="B4" value="30"/>
                    <count group_id="B5" value="352"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="43.8" spread="7.76"/>
                    <measurement group_id="B2" value="43.3" spread="7.75"/>
                    <measurement group_id="B3" value="44.0" spread="7.83"/>
                    <measurement group_id="B4" value="45.5" spread="6.03"/>
                    <measurement group_id="B5" value="43.9" spread="7.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="108"/>
                    <count group_id="B2" value="107"/>
                    <count group_id="B3" value="107"/>
                    <count group_id="B4" value="30"/>
                    <count group_id="B5" value="352"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="56"/>
                    <measurement group_id="B2" value="52"/>
                    <measurement group_id="B3" value="54"/>
                    <measurement group_id="B4" value="11"/>
                    <measurement group_id="B5" value="173"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="52"/>
                    <measurement group_id="B2" value="55"/>
                    <measurement group_id="B3" value="53"/>
                    <measurement group_id="B4" value="19"/>
                    <measurement group_id="B5" value="179"/>
                  </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>White</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="108"/>
                    <count group_id="B2" value="107"/>
                    <count group_id="B3" value="107"/>
                    <count group_id="B4" value="30"/>
                    <count group_id="B5" value="352"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="104"/>
                    <measurement group_id="B2" value="103"/>
                    <measurement group_id="B3" value="105"/>
                    <measurement group_id="B4" value="28"/>
                    <measurement group_id="B5" value="340"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="108"/>
                    <count group_id="B2" value="107"/>
                    <count group_id="B3" value="107"/>
                    <count group_id="B4" value="30"/>
                    <count group_id="B5" value="352"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="108"/>
                    <count group_id="B2" value="107"/>
                    <count group_id="B3" value="107"/>
                    <count group_id="B4" value="30"/>
                    <count group_id="B5" value="352"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="108"/>
                    <count group_id="B2" value="107"/>
                    <count group_id="B3" value="107"/>
                    <count group_id="B4" value="30"/>
                    <count group_id="B5" value="352"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Missing</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="108"/>
                    <count group_id="B2" value="107"/>
                    <count group_id="B3" value="107"/>
                    <count group_id="B4" value="30"/>
                    <count group_id="B5" value="352"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Unified Huntington's Disease Rating Scale - Total Motor Score (UHDRS-TMS)</title>
          <description>The UHDRS TMS assesses all the motor features of HD and includes maximal chorea, maximal dystonia, ocular pursuit, saccade initiation and velocity, dysarthria, tongue protrusion, finger tapping, hand pronation and supination, luria, rigidity, bradykinesia, gait, tandem walking, and retropulsion pull test. Each of these was rated on a scale of 0 (normal motor function) to 4 (severely impaired motor function). TMS score is a sum of individual scores ranging from 0 (normal motor function) to 124 (severely impaired motor function). Lower TMS scores indicate better motor function.</description>
          <population>'Number analyzed' signifies participants evaluable for this parameter.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="108"/>
                    <count group_id="B2" value="107"/>
                    <count group_id="B3" value="106"/>
                    <count group_id="B4" value="30"/>
                    <count group_id="B5" value="351"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26.4" spread="14.63"/>
                    <measurement group_id="B2" value="24.0" spread="13.23"/>
                    <measurement group_id="B3" value="22.1" spread="10.74"/>
                    <measurement group_id="B4" value="26.8" spread="13.75"/>
                    <measurement group_id="B5" value="24.4" spread="13.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Normalized Caudate Volume</title>
          <population>'Number analyzed' signifies participants evaluable for this parameter.</population>
          <units>milliliters (mL)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="106"/>
                    <count group_id="B2" value="103"/>
                    <count group_id="B3" value="102"/>
                    <count group_id="B4" value="28"/>
                    <count group_id="B5" value="339"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6.06" spread="1.857"/>
                    <measurement group_id="B2" value="5.78" spread="1.818"/>
                    <measurement group_id="B3" value="6.02" spread="1.781"/>
                    <measurement group_id="B4" value="5.39" spread="1.218"/>
                    <measurement group_id="B5" value="5.90" spread="1.781"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in UHDRS-TMS at Week 52</title>
        <description>UHDRS is a research tool developed by Huntington Disease (HD) Study Group to provide a uniform assessment of the clinical features and course of HD. Components of the full UHDRS assess motor function, cognition, behaviour, functional abilities, independence scale and total functional capacities. Motor function assessment includes TMS and Total Functional Capacity (TFC) score. The UHDRS TMS assesses all the motor features of HD and includes maximal chorea, maximal dystonia, ocular pursuit, saccade initiation and velocity, dysarthria, tongue protrusion, finger tapping, hand pronation and supination, luria, rigidity, bradykinesia, gait, tandem walking, and retropulsion pull test. Each of these was rated on a scale of 0 (normal motor function) to 4 (severely impaired motor function). TMS score is a sum of individual scores ranging from 0 (normal motor function) to 124 (severely impaired motor function). Lower TMS scores indicate better motor function.</description>
        <time_frame>Baseline, Week 52</time_frame>
        <population>Full analysis set (FAS) included all participants in the ITT population (all randomized participants) who received at least 1 dose of study drug and had at least 1 post-baseline TMS assessment. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received 3 capsules of matching laquinimod placebo, orally once daily for 52 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Laquinimod 0.5 mg</title>
            <description>Participants received 1 capsule of laquinimod 0.5 mg and 2 capsules of matching placebo, orally once daily for 52 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Laquinimod 1.0 mg</title>
            <description>Participants received 2 capsules of laquinimod 0.5 mg (total 1.0 mg laquinimod) and 1 capsule of matching placebo, orally once daily for 52 weeks.</description>
          </group>
          <group group_id="O4">
            <title>Laquinimod 1.5 mg</title>
            <description>Participants received 3 capsules of laquinimod 0.5 mg (total 1.5 mg laquinimod), orally once daily. The treatment of this high dose arm was discontinued as of 10 January 2016.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in UHDRS-TMS at Week 52</title>
          <description>UHDRS is a research tool developed by Huntington Disease (HD) Study Group to provide a uniform assessment of the clinical features and course of HD. Components of the full UHDRS assess motor function, cognition, behaviour, functional abilities, independence scale and total functional capacities. Motor function assessment includes TMS and Total Functional Capacity (TFC) score. The UHDRS TMS assesses all the motor features of HD and includes maximal chorea, maximal dystonia, ocular pursuit, saccade initiation and velocity, dysarthria, tongue protrusion, finger tapping, hand pronation and supination, luria, rigidity, bradykinesia, gait, tandem walking, and retropulsion pull test. Each of these was rated on a scale of 0 (normal motor function) to 4 (severely impaired motor function). TMS score is a sum of individual scores ranging from 0 (normal motor function) to 124 (severely impaired motor function). Lower TMS scores indicate better motor function.</description>
          <population>Full analysis set (FAS) included all participants in the ITT population (all randomized participants) who received at least 1 dose of study drug and had at least 1 post-baseline TMS assessment. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="98"/>
                <count group_id="O2" value="92"/>
                <count group_id="O3" value="95"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.3" spread="8.00"/>
                    <measurement group_id="O2" value="1.4" spread="8.34"/>
                    <measurement group_id="O3" value="2.0" spread="7.27"/>
                    <measurement group_id="O4" value="11.0" spread="7.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Analysis was performed using Mixed Model Repeated Measures model (MMRM) with treatment group (3 levels: placebo, laquinimod 0.5 mg and laquinimod 1 mg), categorical week (4 levels: Weeks 4, 13, 26, and 52), treatment by week interaction, country, TMS baseline value and TMS baseline by week interaction as fixed effects. Unstructured variance-covariance structure was used in the initial model.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.4853</p_value>
            <p_value_desc>Threshold for significance at 0.045 level.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Least square (LS) mean difference</param_type>
            <param_value>0.78</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.42</ci_lower_limit>
            <ci_upper_limit>2.98</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Caudate Volume (Brain Atrophy) at Week 52</title>
        <description>Brain atrophy was assessed using magnetic resonance imaging (MRI) measures of caudate volume. Caudate volume atrophy is a sensitive biomarker in very early HD and correlates with disease progression. Brain atrophy in the caudate refers to the shrinkage in volume, so that a decrease in volume is a positive value, while an increase in volume is a negative value. Percent change in caudate volume at Week 52 was calculated as the change in caudate volume since the baseline visit, divided by the baseline caudate volume and multiplied by 100.</description>
        <time_frame>Baseline, Week 52</time_frame>
        <population>FAS included all participants in the ITT population (all randomized participants) who received at least 1 dose of study drug and had at least 1 post-baseline TMS assessment. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received 3 capsules of matching laquinimod placebo, orally once daily for 52 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Laquinimod 0.5 mg</title>
            <description>Participants received 1 capsule of laquinimod 0.5 mg and 2 capsules of matching placebo, orally once daily for 52 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Laquinimod 1.0 mg</title>
            <description>Participants received 2 capsules of laquinimod 0.5 mg (total 1.0 mg laquinimod) and 1 capsule of matching placebo, orally once daily for 52 weeks.</description>
          </group>
          <group group_id="O4">
            <title>Laquinimod 1.5 mg</title>
            <description>Participants received 3 capsules of laquinimod 0.5 mg (total 1.5 mg laquinimod), orally once daily. The treatment of this high dose arm was discontinued as of 10 January 2016.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Caudate Volume (Brain Atrophy) at Week 52</title>
          <description>Brain atrophy was assessed using magnetic resonance imaging (MRI) measures of caudate volume. Caudate volume atrophy is a sensitive biomarker in very early HD and correlates with disease progression. Brain atrophy in the caudate refers to the shrinkage in volume, so that a decrease in volume is a positive value, while an increase in volume is a negative value. Percent change in caudate volume at Week 52 was calculated as the change in caudate volume since the baseline visit, divided by the baseline caudate volume and multiplied by 100.</description>
          <population>FAS included all participants in the ITT population (all randomized participants) who received at least 1 dose of study drug and had at least 1 post-baseline TMS assessment. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.</population>
          <units>percent change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="87"/>
                <count group_id="O2" value="87"/>
                <count group_id="O3" value="85"/>
                <count group_id="O4" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.13" spread="3.265"/>
                    <measurement group_id="O2" value="4.03" spread="3.275"/>
                    <measurement group_id="O3" value="3.14" spread="3.360"/>
                    <measurement group_id="O4" value="4.11" spread="0.598"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Baseline up to Week 56</time_frame>
      <desc>Safety analysis set included all participants who had received at least 1 dose of study drug.</desc>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>Participants received 3 capsules of matching laquinimod placebo, orally once daily for 52 weeks.</description>
        </group>
        <group group_id="E2">
          <title>Laquinimod 0.5 mg</title>
          <description>Participants received 1 capsule of laquinimod 0.5 mg and 2 capsules of matching placebo, orally once daily for 52 weeks.</description>
        </group>
        <group group_id="E3">
          <title>Laquinimod 1.0 mg</title>
          <description>Participants received 2 capsules of laquinimod 0.5 mg (total 1.0 mg laquinimod) and 1 capsule of matching placebo, orally once daily for 52 weeks.</description>
        </group>
        <group group_id="E4">
          <title>Laquinimod 1.5 mg</title>
          <description>Participants received 3 capsules of laquinimod 0.5 mg (total 1.5 mg laquinimod), orally once daily. The treatment of this high dose arm was discontinued as of 10 January 2016.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA v19.0</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="1" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="107"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="106"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Defect conduction intraventricular</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Small intestinal obstruction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Burn infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Diverticulitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="106"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Gastrointestinal viral infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Osteomyelitis chronic</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="106"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Femur fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Multiple injuries</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Rib fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Road traffic accident</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Skin abrasion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Traumatic liver injury</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </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" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Breast cancer metastatic</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Gastric cancer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cluster headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="106"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Product Issues</title>
            <event_list>
              <event>
                <sub_title>Device dislocation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="106"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="106"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Psychiatric decompensation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Psychotic disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Suicide attempt</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="106"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="106"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Mediastinal haematoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Cutaneous lupus erythematosus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA v19.0</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="62" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="69" subjects_at_risk="107"/>
                <counts group_id="E3" subjects_affected="58" subjects_at_risk="106"/>
                <counts group_id="E4" subjects_affected="19" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
                <counts group_id="E2" events="10" subjects_affected="7" subjects_at_risk="107"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="106"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="108"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="107"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="106"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="108"/>
                <counts group_id="E2" events="14" subjects_affected="12" subjects_at_risk="107"/>
                <counts group_id="E3" events="11" subjects_affected="9" subjects_at_risk="106"/>
                <counts group_id="E4" events="6" subjects_affected="3" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="108"/>
                <counts group_id="E2" events="10" subjects_affected="5" subjects_at_risk="107"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="106"/>
                <counts group_id="E4" events="4" subjects_affected="4" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="108"/>
                <counts group_id="E2" events="10" subjects_affected="7" subjects_at_risk="107"/>
                <counts group_id="E3" events="7" subjects_affected="4" subjects_at_risk="106"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="9" subjects_affected="7" subjects_at_risk="108"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="107"/>
                <counts group_id="E3" events="7" subjects_affected="7" subjects_at_risk="106"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="33" subjects_affected="19" subjects_at_risk="108"/>
                <counts group_id="E2" events="12" subjects_affected="10" subjects_at_risk="107"/>
                <counts group_id="E3" events="13" subjects_affected="10" subjects_at_risk="106"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="108"/>
                <counts group_id="E2" events="5" subjects_affected="3" subjects_at_risk="107"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="106"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="108"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="106"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" events="8" subjects_affected="6" subjects_at_risk="108"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="106"/>
                <counts group_id="E4" events="3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="15" subjects_affected="9" subjects_at_risk="108"/>
                <counts group_id="E2" events="12" subjects_affected="10" subjects_at_risk="107"/>
                <counts group_id="E3" events="7" subjects_affected="5" subjects_at_risk="106"/>
                <counts group_id="E4" events="6" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Ligament sprain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="108"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="106"/>
                <counts group_id="E4" events="4" subjects_affected="2" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="107"/>
                <counts group_id="E3" events="5" subjects_affected="4" subjects_at_risk="106"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Amylase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" events="10" subjects_affected="8" subjects_at_risk="107"/>
                <counts group_id="E3" events="10" subjects_affected="6" subjects_at_risk="106"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Blood folate decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E3" events="6" subjects_affected="6" subjects_at_risk="106"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Haemoglobin decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="106"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Pancreatic enzymes increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="107"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="106"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="108"/>
                <counts group_id="E2" events="7" subjects_affected="5" subjects_at_risk="107"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="106"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="8" subjects_affected="7" subjects_at_risk="108"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="107"/>
                <counts group_id="E3" events="12" subjects_affected="8" subjects_at_risk="106"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Balance disorder</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Chorea</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="108"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="107"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="108"/>
                <counts group_id="E2" events="22" subjects_affected="19" subjects_at_risk="107"/>
                <counts group_id="E3" events="31" subjects_affected="14" subjects_at_risk="106"/>
                <counts group_id="E4" events="5" subjects_affected="5" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="108"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="107"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="106"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="7" subjects_affected="5" subjects_at_risk="108"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="106"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="108"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="107"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="106"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="108"/>
                <counts group_id="E2" events="7" subjects_affected="6" subjects_at_risk="107"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="106"/>
                <counts group_id="E4" events="2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="108"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="107"/>
                <counts group_id="E3" events="7" subjects_affected="6" subjects_at_risk="106"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Director, Clinical Research</name_or_title>
      <organization>Teva Branded Pharmaceutical Products, R&amp;D Inc.</organization>
      <phone>1-888-483-8279</phone>
      <email>USMedInfo@tevapharm.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/NCT02215616
org study id: TV5600-CNS-20007
secondary id: 2014-000418-75
nct id: NCT02215616
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The primary objective of this study is to assess the efficacy of laquinimod as treatment in
      participants with HD after 52 weeks using the Unified Huntington's Disease Rating Scale Total
      Motor Score (UHDRS-TMS or TMS).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Change From Baseline in UHDRS-TMS at Week 52
time frame: Baseline, Week 52
description: UHDRS is a research tool developed by Huntington Disease (HD) Study Group to provide a uniform assessment of the clinical features and course of HD. Components of the full UHDRS assess motor function, cognition, behaviour, functional abilities, independence scale and total functional capacities. Motor function assessment includes TMS and Total Functional Capacity (TFC) score. The UHDRS TMS assesses all the motor features of HD and includes maximal chorea, maximal dystonia, ocular pursuit, saccade initiation and velocity, dysarthria, tongue protrusion, finger tapping, hand pronation and supination, luria, rigidity, bradykinesia, gait, tandem walking, and retropulsion pull test. Each of these was rated on a scale of 0 (normal motor function) to 4 (severely impaired motor function). TMS score is a sum of individual scores ranging from 0 (normal motor function) to 124 (severely impaired motor function). Lower TMS scores indicate better motor function.
measure: Percent Change From Baseline in Caudate Volume (Brain Atrophy) at Week 52
time frame: Baseline, Week 52
description: Brain atrophy was assessed using magnetic resonance imaging (MRI) measures of caudate volume. Caudate volume atrophy is a sensitive biomarker in very early HD and correlates with disease progression. Brain atrophy in the caudate refers to the shrinkage in volume, so that a decrease in volume is a positive value, while an increase in volume is a negative value. Percent change in caudate volume at Week 52 was calculated as the change in caudate volume since the baseline visit, divided by the baseline caudate volume and multiplied by 100.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants will receive 3 capsules of matching laquinimod placebo, orally once daily for 52 weeks.
arm group label: Laquinimod 0.5 mg
arm group type: Experimental
description: Participants will receive 1 capsule of laquinimod 0.5 milligrams (mg) and 2 capsules of matching placebo, orally once daily for 52 weeks.
arm group label: Laquinimod 1.0 mg
arm group type: Experimental
description: Participants will receive 2 capsule of laquinimod 0.5 mg (total 1.0 mg laquinimod) and 1 capsule of matching placebo, orally once daily for 52 weeks.
arm group label: Laquinimod 1.5 mg
arm group type: Experimental
description: Participants will receive 3 capsules of laquinimod 0.5 mg (total 1.5 mg laquinimod), orally once daily.
Note: The treatment of this high dose arm was discontinued as of 10 January 2016.
intervention type: Drug
intervention name: Laquinimod
description: Laquinimod capsules will be administered as per the dose and schedule specified in the respective arms.
arm group label: Laquinimod 0.5 mg
arm group label: Laquinimod 1.0 mg
arm group label: Laquinimod 1.5 mg
intervention type: Drug
intervention name: Placebo
description: Matching laquinimod placebo will be administered as per the schedule specified in the respective arms.
arm group label: Laquinimod 0.5 mg
arm group label: Laquinimod 1.0 mg
arm group label: Placebo
criteria: 
gender: All
minimum age: 21 Years
maximum age: 55 Years
healthy volunteers: No
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country: Canada
country: Czechia
country: Germany
country: Italy
country: Netherlands
country: Portugal
country: Russian Federation
country: Spain
country: United Kingdom
country: United States
country: Czech Republic
country: France
country: India
country: Israel
responsible party type: Sponsor
mesh term: Huntington Disease
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