<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/NCT03761849</url>
  </required_header>
  <id_info>
    <org_study_id>BN40423</org_study_id>
    <secondary_id>GENERATION HD1</secondary_id>
    <nct_id>NCT03761849</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Efficacy and Safety of Intrathecally Administered RO7234292 (RG6042) in Participants With Manifest Huntington's Disease</brief_title>
  <official_title>A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Phase III Clinical Study to Evaluate the Efficacy and Safety of Intrathecally Administered RO7234292 (RG6042) in Patients With Manifest Huntington's Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hoffmann-La Roche</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hoffmann-La Roche</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will evaluate the efficacy, safety, and biomarker effects of RO7234292 (RG6042)&#xD;
      compared with placebo in participants with manifest Huntington's disease (HD).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 23, 2019</start_date>
  <completion_date type="Actual">March 17, 2022</completion_date>
  <primary_completion_date type="Actual">March 17, 2022</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from Baseline in the Composite Unified Huntington's Disease Rating Scale (cUHDRS)</measure>
    <time_frame>Baselined, Week 101</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in the TFC Score</measure>
    <time_frame>Baseline, Week 101</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Total Motor Score (TMS)</measure>
    <time_frame>Baseline, Week 101</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Symbol Digit Modalities Test (SDMT)</measure>
    <time_frame>Baseline, Week 101</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Stroop Word Reading (SWR) Test</measure>
    <time_frame>Baseline, Week 101</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Clinical Global Impression, Severity Scale (CGI-S)</measure>
    <time_frame>Baseline, Week 101</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients with a Decrease From Baseline of &gt;=1 point on the TFC</measure>
    <time_frame>Baseline, Week101</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients With a Decline From Baseline of &gt;=1.2 Points on the cUHDRS</measure>
    <time_frame>Baseline, Week 101</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients With an Unchanged or Improved Score on the Clinical Global Impression, Change Scale (CGI-C) Score</measure>
    <time_frame>Baseline to Week 101</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with Adverse Events</measure>
    <time_frame>Up to 117 Weeks (29 months)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Montreal Cognitive Assessment (MoCA)</measure>
    <time_frame>Screening, Baseline, Weeks 5, 21, 37, 53, 69, 85 and 101 and early treatment termination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Suicidal Ideation or Behavior, as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score</measure>
    <time_frame>Screening, Baseline, Weeks 5, 13, 21, 29, 37, 45, 53, 61, 69, 77, 85, 93, 101, 117, end of treatment for early treatment termination and at early treatment termination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of RO7234292 in Plasma</measure>
    <time_frame>Baseline, Weeks 13, 21, 37, 53, 69, 85, and 101 and early treatment termination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Trough Concentration of RO7234292 in CSF</measure>
    <time_frame>Baseline, Weeks 13, 21, 37, 53, 69, 85, and 101 and early treatment termination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Anti-Drug Antibodies (ADAs)</measure>
    <time_frame>Baseline, Weeks 13, 21, 37, 53, 69, 85, and 101 and early treatment termination and safety follow-up visit</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Titer and Antibody Subtype, determined if ADAs are Identified</measure>
    <time_frame>Baseline, Weeks 13, 21, 37, 53, 69, 85, and 101 and early treatment termination and safety follow-up visit</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in CSF mHTT Protein Level</measure>
    <time_frame>Baseline, Week 101</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Whole and Regional Brain Volumes, as detrmined by structural magnetic resonance imaging (MRI)</measure>
    <time_frame>Baseline, Week 101</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in CSF Neurofilament Light Chain (NfL) Proteint Level</measure>
    <time_frame>Baseline, Week 101</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">899</enrollment>
  <condition>Huntingtons Disease</condition>
  <arm_group>
    <arm_group_label>RO7234292 Q8W</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>RO4234292 is administered intrathecally every 8 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>RO7234292 Q16W</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>RO7234292 is administered intrathecally every 16 weeks. Participants in this arm will also receive placebo at alternate weeks to keep the blind.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo will be administered every 8 weeks by IT injection.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>RO7234292</intervention_name>
    <description>Intrathecal injection</description>
    <arm_group_label>RO7234292 Q16W</arm_group_label>
    <arm_group_label>RO7234292 Q8W</arm_group_label>
    <other_name>Tominersen</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Intrathecal injection</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>RO7234292 Q16W</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Manifest HD diagnosis, defined as a DCL score of 4&#xD;
&#xD;
          -  Independence Scale (IS) score &gt;= 70&#xD;
&#xD;
          -  Genetically confirmed disease by direct DNA testing with a CAP score &gt;400&#xD;
&#xD;
          -  Clinical assessment to ensure individual has intact functional independence at&#xD;
             baseline to maintain self-care and core activities of daily living (ADLs).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any serious medical condition or clinically significant laboratory, or vital sign&#xD;
             abnormality or claustrophobia at screening that, in the investigator's judgment,&#xD;
             precludes the patient's safe participation in and completion of the study&#xD;
&#xD;
          -  Pregnant or breastfeeding, or intending to become pregnant during the study or within&#xD;
             5 months after the final dose of study drug&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>25 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Hoffmann-La Roche</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Uab Medicine</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Barrow Neurological Institute</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85013</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California San Diego</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford Univ Medical Center</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SC3 Research Group, Inc</name>
      <address>
        <city>Pasadena</city>
        <state>California</state>
        <zip>91105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California Davis Medical System</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CenExel Rocky Mountain Clinical Research, LLC</name>
      <address>
        <city>Englewood</city>
        <state>Colorado</state>
        <zip>80113</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Georgetown University; Research Division, Psychiatry</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of South Florida</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33613</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>John Hopkins University School of Medicine</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beth Israel Deaconess Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dent Neurological Institute</name>
      <address>
        <city>Amherst</city>
        <state>New York</state>
        <zip>14226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032-3725</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Texas Health Science Center at Houston; McGovern Medical School</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Utah Clinical Neurosciences Center</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84132</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Evergreen Health Care Center</name>
      <address>
        <city>Kirkland</city>
        <state>Washington</state>
        <zip>98034</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Ramos Mejía</name>
      <address>
        <city>Caba</city>
        <zip>C1221ADC</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>INEBA</name>
      <address>
        <city>Capital Federal</city>
        <zip>C1192AAX</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Britanico de Buenos Aires</name>
      <address>
        <city>Ciudad Autonoma Buenos Aires</city>
        <zip>C1284AEB</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>WESTMEAD HOSPITAL; Deparment of Neurology</name>
      <address>
        <city>Westmead</city>
        <state>New South Wales</state>
        <zip>2145</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Monash Medical Centre</name>
      <address>
        <city>Clayton</city>
        <state>Victoria</state>
        <zip>3168</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Melbourne Hospital; Department of Neurology</name>
      <address>
        <city>Parkville</city>
        <state>Victoria</state>
        <zip>3050</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uniklinik fuer Neurologie, Medizinische Universitaet Innsbruck; Department fuer Neurologie</name>
      <address>
        <city>Innsbruck</city>
        <zip>6020</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Christian-Doppler-Klinik - Universitätsklinikum; Universitätskliniik für Neurologie</name>
      <address>
        <city>Salzburg</city>
        <zip>5020</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Alberta Hospital</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G 1Z1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of British Columbia Hospital; Division of Neurology</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V6T 2B5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>True North Clinical Research-Halifax</name>
      <address>
        <city>Halifax</city>
        <state>Nova Scotia</state>
        <zip>B3S 1N2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre for Movement Disorders</name>
      <address>
        <city>North York</city>
        <state>Ontario</state>
        <zip>M3B 2S7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ottawa Hospital Research Institute</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1Y 4E9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier de l'Université de Montréal (CHUM)</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H2X 0C2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro de Trastornos del Movimiento (CETRAM); CETRAM</name>
      <address>
        <city>LO Espejo</city>
        <zip>9120000</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aarhus Universitetshospital; Neurologisk Afdeling F, Neurogenetisk Afsnit</name>
      <address>
        <city>Aarhus N</city>
        <zip>8200</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rigshospitalet, Hukommelsesklinikken</name>
      <address>
        <city>Koebenhavn Oe</city>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Angers, Batiement Larrey 2, Neurologie</name>
      <address>
        <city>Angers Cedex 9</city>
        <zip>49933</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Henri Mondor; Service de Neurologie</name>
      <address>
        <city>Creteil</city>
        <zip>94010</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Roger Salengro; Service de Neurologie</name>
      <address>
        <city>Lille</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de la Timone - Hopital d Adultes; Service de Neurologie</name>
      <address>
        <city>Marseille</city>
        <zip>13005</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Gui de Chauliac; Neurologie</name>
      <address>
        <city>Montpellier</city>
        <zip>34295</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Pitié Salpêtrère; Département de Génétique et Cytogénétique</name>
      <address>
        <city>Paris</city>
        <zip>75651</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU toulouse - Hôpital Purpan; Departement de Neurologie</name>
      <address>
        <city>Toulouse</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uniklinik RWTH Aachen; Klinik für Neurologie</name>
      <address>
        <city>Aachen</city>
        <zip>52074</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charité - Universitätsmed. Berlin, Klinik für Psychiatrie und Psychotherapie; Abt. Neuropsychiatrie</name>
      <address>
        <city>Berlin</city>
        <zip>10117</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Josef-Hospital, Neurologische Klinik der Ruhr-Uni; Huntington-Center NRW, Abt. Neurodegeneration</name>
      <address>
        <city>Bochum</city>
        <zip>44791</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>German Center for Neurodegenerative Diseases (DZNE)</name>
      <address>
        <city>Bonn</city>
        <zip>53127</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Erlangen, Abteilung Molekulare Neurologie</name>
      <address>
        <city>Erlangen</city>
        <zip>91054</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Schleswig-Holstein / Campus Lübeck; Zentrum für Seltene Erkrankungen</name>
      <address>
        <city>Lübeck</city>
        <zip>23538</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>George-Huntington- Institut GmbH; Technologiepark Münster</name>
      <address>
        <city>Münster</city>
        <zip>48149</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Ulm; Klinik für Neurologie</name>
      <address>
        <city>Ulm</city>
        <zip>89081</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRCCS Istituto delle Scienze Neurologiche; UOC Clinica Neurologica</name>
      <address>
        <city>Bologna</city>
        <state>Emilia-Romagna</state>
        <zip>40139</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Sant'Andrea; UOC Neurologia</name>
      <address>
        <city>Roma</city>
        <state>Lazio</state>
        <zip>00189</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Irccs A.O.U.San Martino Ist; Dinogmi</name>
      <address>
        <city>Genova</city>
        <state>Liguria</state>
        <zip>16132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS Istituto Neurologico Carlo Besta; U.O.C. Genetica Medica-Neurogenetica</name>
      <address>
        <city>Milano</city>
        <state>Lombardia</state>
        <zip>20133</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRCCS Casa Sollievo Della Sofferenza; Unità Ricerca e Cura Huntington e Malattie Rare</name>
      <address>
        <city>San Giovanni Rotondo (FG)</city>
        <state>Puglia</state>
        <zip>71013</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O.U. Careggi; Diaprtimento Scienze Neurologiche e Psichiatriche</name>
      <address>
        <city>Firenze</city>
        <state>Toscana</state>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Hospital Organization Sagamihara National Hospital</name>
      <address>
        <city>Kanagawa</city>
        <zip>252-0392</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kuwana City Medical Center</name>
      <address>
        <city>Mie</city>
        <zip>511-0061</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Hospital Organization Niigata National Hospital</name>
      <address>
        <city>Niigata</city>
        <zip>945-8585</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Okayama University Graduate School of Medicine, Densitry and Pharmaceutical Sciences.</name>
      <address>
        <city>Okayama</city>
        <zip>700-8558</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Osaka General Medical Center</name>
      <address>
        <city>Osaka</city>
        <zip>558-8558</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Center of Neurology and Psychiatry</name>
      <address>
        <city>Tokyo</city>
        <zip>187-8551</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitair Medisch Centrum Groningen</name>
      <address>
        <city>Groningen</city>
        <zip>9713 GZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LUMC</name>
      <address>
        <city>Leiden</city>
        <zip>2333 ZA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Auckland DHB - Neurlogy Department; Neurology Department</name>
      <address>
        <city>Auckland</city>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New Zealand Brain Research Institute</name>
      <address>
        <city>Christchurch</city>
        <zip>8011</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wellington Hospital; Department of Neurology</name>
      <address>
        <city>Wellington</city>
        <zip>6021</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Szpital Sw. Wojciecha; Oddzial Neurologiczny</name>
      <address>
        <city>Gdańsk</city>
        <zip>80-462</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Krakowska Akademia Neurologii Sp z o.o. Centrum Neurologii K</name>
      <address>
        <city>Krakow</city>
        <zip>31-505</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instytut Psychiatrii i Neurologii</name>
      <address>
        <city>Warszawa</city>
        <zip>02-957</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>FSBHI Siberian Clinical Center of the Federal Medical and Biological Agency</name>
      <address>
        <city>Krasnoyarsk</city>
        <state>Krasnojarsk</state>
        <zip>660037</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Center of Neurology; Neurology Department #5</name>
      <address>
        <city>Moskva</city>
        <state>Moskovskaja Oblast</state>
        <zip>125367</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Сlinical hospital at Kazan station, Republican Center for Movement Disorders and Botulinum Therapy</name>
      <address>
        <city>Kazan</city>
        <state>Tatarstan</state>
        <zip>420061</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Cruces; Servicio de Neurologia</name>
      <address>
        <city>Barakaldo</city>
        <state>Vizcaya</state>
        <zip>48903</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Badajoz; Servicio de Neurología</name>
      <address>
        <city>Badajoz</city>
        <zip>06080</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinic Servicio de Neurologia</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de la Santa Creu i Sant Pau; Servicio de Neurologia</name>
      <address>
        <city>Barcelona</city>
        <zip>08041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Burgos. Servicio de Neurología</name>
      <address>
        <city>Burgos</city>
        <zip>09006</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Ramon y Cajal; Servicio de Neurologia</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fundacion Jimenez Diaz; Servicio de Neurología</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen Macarena; Servicio de Neurologia</name>
      <address>
        <city>Sevilla</city>
        <zip>41009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario la Fe; Servicio de Neurologia</name>
      <address>
        <city>Valencia</city>
        <zip>46026</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsspital Basel; Neurologie</name>
      <address>
        <city>Basel</city>
        <zip>4031</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neurozentrum Siloah</name>
      <address>
        <city>Gümligen</city>
        <zip>3073</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aberdeen Royal Infirmary; Medical Genectics</name>
      <address>
        <city>Aberdeen</city>
        <zip>AB25 2ZD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen Elizabeth Hospital</name>
      <address>
        <city>Birmingham</city>
        <zip>B15 2TH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cambridge Centre for Brain Repair; Department of Clinical Nuerosciences, Addenbrookes Hospital</name>
      <address>
        <city>Cambridge</city>
        <zip>CB2 0SP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital of Wales; Division of Psychological Medicine and Clinical Neurosciences</name>
      <address>
        <city>Cardiff</city>
        <zip>CF14 4XW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen Elizabeth University Hospital Glasgow</name>
      <address>
        <city>Glasgow</city>
        <zip>G51 4TF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Leeds General Infirmary</name>
      <address>
        <city>Leeds</city>
        <zip>LS1 3EX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Hospital For Neurology and Neurosurgery</name>
      <address>
        <city>London</city>
        <zip>WC1N 3BG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Central Manchester University Hospitals NHS Foundation Trust; Manchester Centre for Genomic Medicine</name>
      <address>
        <city>Manchester</city>
        <zip>M13 9WL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>John Radcliffe Hospital</name>
      <address>
        <city>Oxford</city>
        <zip>OX3 9DU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Hallamshire Hospital</name>
      <address>
        <city>Sheffield</city>
        <zip>S10 2JF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Southampton NHS Foundation Trust</name>
      <address>
        <city>Southhampton</city>
        <zip>SO16 6YD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Australia</country>
    <country>Austria</country>
    <country>Canada</country>
    <country>Chile</country>
    <country>Denmark</country>
    <country>France</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Japan</country>
    <country>Netherlands</country>
    <country>New Zealand</country>
    <country>Poland</country>
    <country>Russian Federation</country>
    <country>Spain</country>
    <country>Switzerland</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>China</country>
  </removed_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>November 30, 2018</study_first_submitted>
  <study_first_submitted_qc>November 30, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 3, 2018</study_first_posted>
  <last_update_submitted>September 21, 2022</last_update_submitted>
  <last_update_submitted_qc>September 21, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 22, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HD, RG6042, intrathecal, ASO, antisense oligonucleotide</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Huntington Disease</mesh_term>
  </condition_browse>
  <pending_results>
    <submitted>March 16, 2023</submitted>
    <returned>April 11, 2023</returned>
    <submitted>May 4, 2023</submitted>
    <returned>June 2, 2023</returned>
    <submitted>June 22, 2023</submitted>
    <returned>July 13, 2023</returned>
    <submitted>August 7, 2023</submitted>
    <returned>August 29, 2023</returned>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03761849
org study id: BN40423
secondary id: GENERATION HD1
nct id: NCT03761849
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study will evaluate the efficacy, safety, and biomarker effects of RO7234292 (RG6042)
      compared with placebo in participants with manifest Huntington's disease (HD).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change from Baseline in the Composite Unified Huntington's Disease Rating Scale (cUHDRS)
time frame: Baselined, Week 101
measure: Change From Baseline in the TFC Score
time frame: Baseline, Week 101
measure: Change From Baseline in Total Motor Score (TMS)
time frame: Baseline, Week 101
measure: Change From Baseline in Symbol Digit Modalities Test (SDMT)
time frame: Baseline, Week 101
measure: Change From Baseline in Stroop Word Reading (SWR) Test
time frame: Baseline, Week 101
measure: Change From Baseline in the Clinical Global Impression, Severity Scale (CGI-S)
time frame: Baseline, Week 101
measure: Percentage of Patients with a Decrease From Baseline of >=1 point on the TFC
time frame: Baseline, Week101
measure: Percentage of Patients With a Decline From Baseline of >=1.2 Points on the cUHDRS
time frame: Baseline, Week 101
measure: Percentage of Patients With an Unchanged or Improved Score on the Clinical Global Impression, Change Scale (CGI-C) Score
time frame: Baseline to Week 101
measure: Percentage of Participants with Adverse Events
time frame: Up to 117 Weeks (29 months)
measure: Change From Baseline in Montreal Cognitive Assessment (MoCA)
time frame: Screening, Baseline, Weeks 5, 21, 37, 53, 69, 85 and 101 and early treatment termination
measure: Percentage of Participants With Suicidal Ideation or Behavior, as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score
time frame: Screening, Baseline, Weeks 5, 13, 21, 29, 37, 45, 53, 61, 69, 77, 85, 93, 101, 117, end of treatment for early treatment termination and at early treatment termination
measure: Concentration of RO7234292 in Plasma
time frame: Baseline, Weeks 13, 21, 37, 53, 69, 85, and 101 and early treatment termination
measure: Trough Concentration of RO7234292 in CSF
time frame: Baseline, Weeks 13, 21, 37, 53, 69, 85, and 101 and early treatment termination
measure: Incidence of Anti-Drug Antibodies (ADAs)
time frame: Baseline, Weeks 13, 21, 37, 53, 69, 85, and 101 and early treatment termination and safety follow-up visit
measure: Titer and Antibody Subtype, determined if ADAs are Identified
time frame: Baseline, Weeks 13, 21, 37, 53, 69, 85, and 101 and early treatment termination and safety follow-up visit
measure: Change From Baseline in CSF mHTT Protein Level
time frame: Baseline, Week 101
measure: Change From Baseline in Whole and Regional Brain Volumes, as detrmined by structural magnetic resonance imaging (MRI)
time frame: Baseline, Week 101
measure: Change From Baseline in CSF Neurofilament Light Chain (NfL) Proteint Level
time frame: Baseline, Week 101
arm group label: RO7234292 Q8W
arm group type: Experimental
description: RO4234292 is administered intrathecally every 8 weeks.
arm group label: RO7234292 Q16W
arm group type: Experimental
description: RO7234292 is administered intrathecally every 16 weeks. Participants in this arm will also receive placebo at alternate weeks to keep the blind.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo will be administered every 8 weeks by IT injection.
intervention type: Drug
intervention name: RO7234292
description: Intrathecal injection
arm group label: RO7234292 Q16W
arm group label: RO7234292 Q8W
other name: Tominersen
intervention type: Drug
intervention name: Placebo
description: Intrathecal injection
arm group label: Placebo
arm group label: RO7234292 Q16W
criteria: 
gender: All
minimum age: 25 Years
maximum age: 65 Years
healthy volunteers: No
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Argentina
country: Australia
country: Austria
country: Canada
country: Chile
country: Denmark
country: France
country: Germany
country: Italy
country: Japan
country: Netherlands
country: New Zealand
country: Poland
country: Russian Federation
country: Spain
country: Switzerland
country: United Kingdom
country: United States
country: China
responsible party type: Sponsor
mesh term: Huntington Disease
submitted: March 16, 2023
returned: April 11, 2023
submitted: May 4, 2023
returned: June 2, 2023
submitted: June 22, 2023
returned: July 13, 2023
submitted: August 7, 2023
returned: August 29, 2023