A Study to Evaluate the Efficacy and Safety of Intrathecally Administered RO7234292 (RG6042) in Participants With Manifest Huntington's Disease
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT03761849 |
Recruitment Status :
Active, not recruiting
First Posted : December 3, 2018
Last Update Posted : June 21, 2022
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Huntingtons Disease | Drug: RO7234292 Drug: Placebo | Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 899 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
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 |
Actual Study Start Date : | January 23, 2019 |
Actual Primary Completion Date : | March 17, 2022 |
Estimated Study Completion Date : | March 17, 2023 |

Arm | Intervention/treatment |
---|---|
Experimental: RO7234292 Q8W
RO4234292 is administered intrathecally every 8 weeks.
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Drug: RO7234292
Intrathecal injection
Other Name: Tominersen |
Experimental: RO7234292 Q16W
RO7234292 is administered intrathecally every 16 weeks. Participants in this arm will also receive placebo at alternate weeks to keep the blind.
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Drug: RO7234292
Intrathecal injection
Other Name: Tominersen Drug: Placebo Intrathecal injection |
Placebo Comparator: Placebo
Placebo will be administered every 8 weeks by IT injection.
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Drug: Placebo
Intrathecal injection |
- Change from Baseline in the Composite Unified Huntington's Disease Rating Scale (cUHDRS) [ Time Frame: Baselined, Week 101 ]
- Change From Baseline in the TFC Score [ Time Frame: Baseline, Week 101 ]
- Change From Baseline in Total Motor Score (TMS) [ Time Frame: Baseline, Week 101 ]
- Change From Baseline in Symbol Digit Modalities Test (SDMT) [ Time Frame: Baseline, Week 101 ]
- Change From Baseline in Stroop Word Reading (SWR) Test [ Time Frame: Baseline, Week 101 ]
- Change From Baseline in the Clinical Global Impression, Severity Scale (CGI-S) [ Time Frame: Baseline, Week 101 ]
- Percentage of Patients with a Decrease From Baseline of >=1 point on the TFC [ Time Frame: Baseline, Week101 ]
- Percentage of Patients With a Decline From Baseline of >=1.2 Points on the cUHDRS [ Time Frame: Baseline, Week 101 ]
- 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 ]
- Percentage of Participants with Adverse Events [ Time Frame: Up to 117 Weeks (29 months) ]
- 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 ]
- 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 ]
- Concentration of RO7234292 in Plasma [ Time Frame: Baseline, Weeks 13, 21, 37, 53, 69, 85, and 101 and early treatment termination ]
- Trough Concentration of RO7234292 in CSF [ Time Frame: Baseline, Weeks 13, 21, 37, 53, 69, 85, and 101 and early treatment termination ]
- 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 ]
- 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 ]
- Change From Baseline in CSF mHTT Protein Level [ Time Frame: Baseline, Week 101 ]
- Change From Baseline in Whole and Regional Brain Volumes, as detrmined by structural magnetic resonance imaging (MRI) [ Time Frame: Baseline, Week 101 ]
- Change From Baseline in CSF Neurofilament Light Chain (NfL) Proteint Level [ Time Frame: Baseline, Week 101 ]

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 25 Years to 65 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Manifest HD diagnosis, defined as a DCL score of 4
- Independence Scale (IS) score >= 70
- Genetically confirmed disease by direct DNA testing with a CAP score >400
- Clinical assessment to ensure individual has intact functional independence at baseline to maintain self-care and core activities of daily living (ADLs).
Exclusion Criteria:
- Any serious medical condition or clinically significant laboratory, or vital sign abnormality or claustrophobia at screening that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study
- Pregnant or breastfeeding, or intending to become pregnant during the study or within 5 months after the final dose of study drug

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03761849

United States, Alabama | |
Uab Medicine | |
Birmingham, Alabama, United States, 35294 | |
United States, Arizona | |
Barrow Neurological Institute | |
Phoenix, Arizona, United States, 85013 | |
United States, California | |
University of California San Diego | |
La Jolla, California, United States, 92093 | |
Stanford Univ Medical Center | |
Palo Alto, California, United States, 94304 | |
SC3 Research Group, Inc | |
Pasadena, California, United States, 91105 | |
University of California Davis Medical System | |
Sacramento, California, United States, 95817 | |
United States, Colorado | |
CenExel Rocky Mountain Clinical Research, LLC | |
Englewood, Colorado, United States, 80113 | |
United States, District of Columbia | |
Georgetown University; Research Division, Psychiatry | |
Washington, District of Columbia, United States, 20007 | |
United States, Florida | |
University of South Florida | |
Tampa, Florida, United States, 33613 | |
United States, Illinois | |
Northwestern University | |
Chicago, Illinois, United States, 60611 | |
United States, Maryland | |
John Hopkins University School of Medicine | |
Baltimore, Maryland, United States, 21287 | |
United States, Massachusetts | |
Beth Israel Deaconess Medical Center | |
Boston, Massachusetts, United States, 02215 | |
United States, Missouri | |
Washington University School of Medicine | |
Saint Louis, Missouri, United States, 63110 | |
United States, New York | |
Dent Neurological Institute | |
Amherst, New York, United States, 14226 | |
Columbia University | |
New York, New York, United States, 10032-3725 | |
United States, Pennsylvania | |
University of Pittsburgh | |
Pittsburgh, Pennsylvania, United States, 15213 | |
United States, Tennessee | |
Vanderbilt University Medical Center | |
Nashville, Tennessee, United States, 37232 | |
United States, Texas | |
The University of Texas Health Science Center at Houston; McGovern Medical School | |
Houston, Texas, United States, 77030 | |
United States, Utah | |
University of Utah Clinical Neurosciences Center | |
Salt Lake City, Utah, United States, 84132 | |
United States, Washington | |
Evergreen Health Care Center | |
Kirkland, Washington, United States, 98034 | |
Argentina | |
Hospital Ramos Mejía | |
Caba, Argentina, C1221ADC | |
INEBA | |
Capital Federal, Argentina, C1192AAX | |
Hospital Britanico de Buenos Aires | |
Ciudad Autonoma Buenos Aires, Argentina, C1284AEB | |
Australia, New South Wales | |
WESTMEAD HOSPITAL; Deparment of Neurology | |
Westmead, New South Wales, Australia, 2145 | |
Australia, Victoria | |
Monash Medical Centre | |
Clayton, Victoria, Australia, 3168 | |
Royal Melbourne Hospital; Department of Neurology | |
Parkville, Victoria, Australia, 3050 | |
Austria | |
Uniklinik fuer Neurologie, Medizinische Universitaet Innsbruck; Department fuer Neurologie | |
Innsbruck, Austria, 6020 | |
Christian-Doppler-Klinik - Universitätsklinikum; Universitätskliniik für Neurologie | |
Salzburg, Austria, 5020 | |
Canada, Alberta | |
University of Alberta Hospital | |
Edmonton, Alberta, Canada, T6G 1Z1 | |
Canada, British Columbia | |
University of British Columbia Hospital; Division of Neurology | |
Vancouver, British Columbia, Canada, V6T 2B5 | |
Canada, Nova Scotia | |
True North Clinical Research-Halifax | |
Halifax, Nova Scotia, Canada, B3S 1N2 | |
Canada, Ontario | |
Centre for Movement Disorders | |
North York, Ontario, Canada, M3B 2S7 | |
Ottawa Hospital Research Institute | |
Ottawa, Ontario, Canada, K1Y 4E9 | |
Canada, Quebec | |
Centre Hospitalier de l'Université de Montréal (CHUM) | |
Montreal, Quebec, Canada, H2X 0C2 | |
Chile | |
Centro de Trastornos del Movimiento (CETRAM); CETRAM | |
LO Espejo, Chile, 9120000 | |
Denmark | |
Aarhus Universitetshospital; Neurologisk Afdeling F, Neurogenetisk Afsnit | |
Aarhus N, Denmark, 8200 | |
Rigshospitalet, Hukommelsesklinikken | |
Koebenhavn Oe, Denmark, 2100 | |
France | |
CHU Angers, Batiement Larrey 2, Neurologie | |
Angers Cedex 9, France, 49933 | |
Hopital Henri Mondor; Service de Neurologie | |
Creteil, France, 94010 | |
Hopital Roger Salengro; Service de Neurologie | |
Lille, France | |
CHU de la Timone - Hopital d Adultes; Service de Neurologie | |
Marseille, France, 13005 | |
Hopital Gui de Chauliac; Neurologie | |
Montpellier, France, 34295 | |
Hôpital Pitié Salpêtrère; Département de Génétique et Cytogénétique | |
Paris, France, 75651 | |
CHU toulouse - Hôpital Purpan; Departement de Neurologie | |
Toulouse, France, 31059 | |
Germany | |
Uniklinik RWTH Aachen; Klinik für Neurologie | |
Aachen, Germany, 52074 | |
Charité - Universitätsmed. Berlin, Klinik für Psychiatrie und Psychotherapie; Abt. Neuropsychiatrie | |
Berlin, Germany, 10117 | |
St. Josef-Hospital, Neurologische Klinik der Ruhr-Uni; Huntington-Center NRW, Abt. Neurodegeneration | |
Bochum, Germany, 44791 | |
German Center for Neurodegenerative Diseases (DZNE) | |
Bonn, Germany, 53127 | |
Universitätsklinikum Erlangen, Abteilung Molekulare Neurologie | |
Erlangen, Germany, 91054 | |
Universitätsklinikum Schleswig-Holstein / Campus Lübeck; Zentrum für Seltene Erkrankungen | |
Lübeck, Germany, 23538 | |
George-Huntington- Institut GmbH; Technologiepark Münster | |
Münster, Germany, 48149 | |
Universitätsklinikum Ulm; Klinik für Neurologie | |
Ulm, Germany, 89081 | |
Italy | |
IRCCS Istituto delle Scienze Neurologiche; UOC Clinica Neurologica | |
Bologna, Emilia-Romagna, Italy, 40139 | |
Azienda Ospedaliera Sant'Andrea; UOC Neurologia | |
Roma, Lazio, Italy, 00189 | |
Irccs A.O.U.San Martino Ist; Dinogmi | |
Genova, Liguria, Italy, 16132 | |
Fondazione IRCCS Istituto Neurologico Carlo Besta; U.O.C. Genetica Medica-Neurogenetica | |
Milano, Lombardia, Italy, 20133 | |
IRCCS Casa Sollievo Della Sofferenza; Unità Ricerca e Cura Huntington e Malattie Rare | |
San Giovanni Rotondo (FG), Puglia, Italy, 71013 | |
A.O.U. Careggi; Diaprtimento Scienze Neurologiche e Psichiatriche | |
Firenze, Toscana, Italy | |
Japan | |
National Hospital Organization Sagamihara National Hospital | |
Kanagawa, Japan, 252-0392 | |
Kuwana City Medical Center | |
Mie, Japan, 511-0061 | |
National Hospital Organization Niigata National Hospital | |
Niigata, Japan, 945-8585 | |
Okayama University Graduate School of Medicine, Densitry and Pharmaceutical Sciences. | |
Okayama, Japan, 700-8558 | |
Osaka General Medical Center | |
Osaka, Japan, 558-8558 | |
National Center of Neurology and Psychiatry | |
Tokyo, Japan, 187-8551 | |
Netherlands | |
Universitair Medisch Centrum Groningen | |
Groningen, Netherlands, 9713 GZ | |
LUMC | |
Leiden, Netherlands, 2333 ZA | |
New Zealand | |
Auckland DHB - Neurlogy Department; Neurology Department | |
Auckland, New Zealand | |
New Zealand Brain Research Institute | |
Christchurch, New Zealand, 8011 | |
Wellington Hospital; Department of Neurology | |
Wellington, New Zealand, 6021 | |
Poland | |
Szpital Sw. Wojciecha; Oddzial Neurologiczny | |
Gdańsk, Poland, 80-462 | |
Krakowska Akademia Neurologii Sp z o.o. Centrum Neurologii K | |
Krakow, Poland, 31-505 | |
Instytut Psychiatrii i Neurologii | |
Warszawa, Poland, 02-957 | |
Russian Federation | |
FSBHI Siberian Clinical Center of the Federal Medical and Biological Agency | |
Krasnoyarsk, Krasnojarsk, Russian Federation, 660037 | |
Research Center of Neurology; Neurology Department #5 | |
Moskva, Moskovskaja Oblast, Russian Federation, 125367 | |
Сlinical hospital at Kazan station, Republican Center for Movement Disorders and Botulinum Therapy | |
Kazan, Tatarstan, Russian Federation, 420061 | |
Spain | |
Hospital de Cruces; Servicio de Neurologia | |
Barakaldo, Vizcaya, Spain, 48903 | |
Hospital Universitario de Badajoz; Servicio de Neurología | |
Badajoz, Spain, 06080 | |
Hospital Clinic Servicio de Neurologia | |
Barcelona, Spain, 08036 | |
Hospital de la Santa Creu i Sant Pau; Servicio de Neurologia | |
Barcelona, Spain, 08041 | |
Hospital Universitario de Burgos. Servicio de Neurología | |
Burgos, Spain, 09006 | |
Hospital Ramon y Cajal; Servicio de Neurologia | |
Madrid, Spain, 28034 | |
Fundacion Jimenez Diaz; Servicio de Neurología | |
Madrid, Spain, 28040 | |
Hospital Universitario Virgen Macarena; Servicio de Neurologia | |
Sevilla, Spain, 41009 | |
Hospital Universitario la Fe; Servicio de Neurologia | |
Valencia, Spain, 46026 | |
Switzerland | |
Universitätsspital Basel; Neurologie | |
Basel, Switzerland, 4031 | |
Neurozentrum Siloah | |
Gümligen, Switzerland, 3073 | |
United Kingdom | |
Aberdeen Royal Infirmary; Medical Genectics | |
Aberdeen, United Kingdom, AB25 2ZD | |
Queen Elizabeth Hospital | |
Birmingham, United Kingdom, B15 2TH | |
Cambridge Centre for Brain Repair; Department of Clinical Nuerosciences, Addenbrookes Hospital | |
Cambridge, United Kingdom, CB2 0SP | |
University Hospital of Wales; Division of Psychological Medicine and Clinical Neurosciences | |
Cardiff, United Kingdom, CF14 4XW | |
Queen Elizabeth University Hospital Glasgow | |
Glasgow, United Kingdom, G51 4TF | |
Leeds General Infirmary | |
Leeds, United Kingdom, LS1 3EX | |
National Hospital For Neurology and Neurosurgery | |
London, United Kingdom, WC1N 3BG | |
Central Manchester University Hospitals NHS Foundation Trust; Manchester Centre for Genomic Medicine | |
Manchester, United Kingdom, M13 9WL | |
John Radcliffe Hospital | |
Oxford, United Kingdom, OX3 9DU | |
Royal Hallamshire Hospital | |
Sheffield, United Kingdom, S10 2JF | |
University Hospital Southampton NHS Foundation Trust | |
Southhampton, United Kingdom, SO16 6YD |
Study Director: | Clinical Trials | Hoffmann-La Roche |
Responsible Party: | Hoffmann-La Roche |
ClinicalTrials.gov Identifier: | NCT03761849 |
Other Study ID Numbers: |
BN40423 GENERATION HD1 ( Other Identifier: Hoffmann-La Roche ) |
First Posted: | December 3, 2018 Key Record Dates |
Last Update Posted: | June 21, 2022 |
Last Verified: | June 2022 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
HD, RG6042, intrathecal, ASO, antisense oligonucleotide |
Huntington Disease Basal Ganglia Diseases Brain Diseases Central Nervous System Diseases Nervous System Diseases Dementia Chorea Dyskinesias |
Movement Disorders Heredodegenerative Disorders, Nervous System Neurodegenerative Diseases Genetic Diseases, Inborn Cognition Disorders Neurocognitive Disorders Mental Disorders |