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A Study to Evaluate the Efficacy and Safety of Intrathecally Administered RO7234292 (RG6042) in Patients With Manifest Huntington's Disease

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ClinicalTrials.gov Identifier: NCT03761849
Recruitment Status : Terminated (Based on the independent Data Monitoring Committee's recommendation that all dosing be stopped and patients continue to be followed for safety and efficacy outcomes as per protocol, without study drug administration from 22 March 2021.)
First Posted : December 3, 2018
Last Update Posted : April 26, 2021
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
This study will evaluate the efficacy, safety, and biomarker effects of RO7234292 (RG6042) compared with placebo in patients with manifest Huntington's disease (HD).

Condition or disease Intervention/treatment Phase
Huntingtons Disease Drug: RO7234292 Drug: Placebo Phase 3

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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 26, 2021
Actual Study Completion Date : March 26, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: RO7234292 Q8W
RO4234292 is administered intrathecally every 8 weeks.
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.
Drug: RO7234292
Intrathecal injection
Other Name: Tominersen

Drug: Placebo
Intrathecal injection

Placebo Comparator: Placebo
Placebo will be administered every 8 weeks by IT injection.
Drug: Placebo
Intrathecal injection




Primary Outcome Measures :
  1. Change from Baseline in the Composite Unified Huntington's Disease Rating Scale (cUHDRS) [ Time Frame: Baselined, Week 101 ]
  2. Change From Baseline in the TFC Score [ Time Frame: Baseline, Week 101 ]

Secondary Outcome Measures :
  1. Change From Baseline in Total Motor Score (TMS) [ Time Frame: Baseline, Week 101 ]
  2. Change From Baseline in Symbol Digit Modalities Test (SDMT) [ Time Frame: Baseline, Week 101 ]
  3. Change From Baseline in Stroop Word Reading (SWR) Test [ Time Frame: Baseline, Week 101 ]
  4. Change From Baseline in the Clinical Global Impression, Severity Scale (CGI-S) [ Time Frame: Baseline, Week 101 ]
  5. Percentage of Patients with a Decrease From Baseline of >=1 point on the TFC [ Time Frame: Baseline, Week101 ]
  6. Percentage of Patients With a Decline From Baseline of >=1.2 Points on the cUHDRS [ Time Frame: Baseline, Week 101 ]
  7. 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 ]
  8. Percentage of Participants with Adverse Events [ Time Frame: Up to 117 Weeks (29 months) ]
  9. 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 ]
  10. 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 ]
  11. Concentration of RO7234292 in Plasma [ Time Frame: Baseline, Weeks 13, 21, 37, 53, 69, 85, and 101 and early treatment termination ]
  12. Trough Concentration of RO7234292 in CSF [ Time Frame: Baseline, Weeks 13, 21, 37, 53, 69, 85, and 101 and early treatment termination ]
  13. 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 ]
  14. 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 ]
  15. Change From Baseline in CSF mHTT Protein Level [ Time Frame: Baseline, Week 101 ]
  16. Change From Baseline in Whole and Regional Brain Volumes, as detrmined by structural magnetic resonance imaging (MRI) [ Time Frame: Baseline, Week 101 ]
  17. Change From Baseline in CSF Neurofilament Light Chain (NfL) Proteint Level [ Time Frame: Baseline, Week 101 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   25 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

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


Locations
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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
Rocky Mountain Movement Disorders Center
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, C1192
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
Santiago, Chile, 8380815
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, 2300 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
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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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: April 26, 2021
Last Verified: April 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hoffmann-La Roche:
HD, RG6042, intrathecal, ASO, antisense oligonucleotide
Additional relevant MeSH terms:
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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