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

• ClinicalTrials.gov Identifier: NCT03761849
• Recruitment Status: Active, not recruiting
• First Posted: December 3, 2018
• Last Update Posted: June 21, 2022
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief Summary:

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

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

Study Design

• 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

Arms and Interventions

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

Outcome Measures

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 ]

Eligibility Criteria

• 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

Contacts and Locations

Locations

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

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Rodrigues FB, Ferreira JJ, Wild EJ. Huntington's Disease Clinical Trials Corner: June 2019. J Huntingtons Dis. 2019;8(3):363-371. doi: 10.3233/JHD-199003.

Rodrigues FB, Quinn L, Wild EJ. Huntington's Disease Clinical Trials Corner: January 2019. J Huntingtons Dis. 2019;8(1):115-125. doi: 10.3233/JHD-190001. Review.

• 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
• 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

Keywords provided by Hoffmann-La Roche:

HD, RG6042, intrathecal, ASO, antisense oligonucleotide

Additional relevant MeSH terms:

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