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

NCT03761849 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: BN40423GENERATION HD1
• Study Type: interventional
• Target: 899
• Locations: 17 countries
• Sites: 93

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)

Conditions

Huntingtons Disease

Keywords

HD, RG6042, intrathecal, ASO, antisense oligonucleotide

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in the Composite Unified Huntington's Disease Rating Scale (cUHDRS) Score-Z Score

  cUHDRS includes the Total Functional Capacity (range, 0-13; higher score means better functioning), Total Motor Score (range, 0-124; higher score means worse motor severity), Symbol Digit Modality Test (range, 0-110, correctly paired numbers-symbols in 90 seconds; higher score means better cognitive performance), and Stroop Word Reading (range, 0-no max value, correctly read colour words in 45 seconds; higher score means better cognitive performance) scores. A z-score for each test is calculated, which alone can be used to describe relationship between an individual's test score and the mean score of a target population. A z-score of 0 is the mean, and ±1 is 1 standard deviation from the mean. For cUHDRS, z-scores of each test are summed, whereby a higher cUHDRS score is better (score of -3.06-no max value) and a change of ≥1.2 is a meaningful worsening, shown to track functional decline.

  Weeks 21 for ODC and 69 for NDC

• Change From Baseline in the Total Functional Capacity (TFC) Score

  Total Functional Capacity (TFC) Scores are reported at Weeks 21 and 69. Total Functional Capacity Score ranges from 0 to 13, with a higher score representing better functioning.

  Weeks 21 for ODC and 69 for NDC

Secondary Outcomes (17)

• Change From Baseline in Total Motor Score (TMS)

  Weeks 21 for ODC and 69 for NDC

• Change From Baseline in Symbol Digit Modalities Test (SDMT) Scores' Least Squares Mean Values

  Weeks 21 for ODC and 69 NDC

• Change From Baseline in Stroop Word Reading (SWR) Test Scores' Least Squares Mean Values

  Weeks 21 for ODC and 69 for NDC

• Change From Baseline in the Clinical Global Impression, Severity Scale (CGI-S) Scores' Least Squares Mean Values

  Week 69 for NDC Only

• Percentage of Patients With a Decrease From Baseline of >=1 Point on the Total Functional Capacity (TFC) Score

  Week 69 for NDC only

Study Arms (3)

RO7234292 Q8W

EXPERIMENTAL

RO4234292 is administered intrathecally every 8 weeks.

Drug: RO7234292

RO7234292 Q16W

EXPERIMENTAL

RO7234292 is administered intrathecally every 16 weeks. Participants in this arm will also receive placebo at alternate weeks to keep the blind.

Drug: RO7234292; Drug: Placebo

Placebo

PLACEBO COMPARATOR

Placebo will be administered every 8 weeks by IT injection.

Drug: Placebo

Interventions

RO7234292 DRUG

Intrathecal injection

Also known as: Tominersen

RO7234292 Q16W; RO7234292 Q8W

Placebo DRUG

Intrathecal injection

Placebo; RO7234292 Q16W

Eligibility Criteria

• Age: 25 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (96)

Uab Medicine

Birmingham, Alabama, 35294, United States

Location

Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

Location

University of California San Diego

La Jolla, California, 92037-1337, United States

Location

Stanford Univ Medical Center

Palo Alto, California, 94304, United States

Location

SC3 Research Group, Inc

Pasadena, California, 91105, United States

Location

University of California Davis Medical System

Sacramento, California, 95817, United States

Location

CenExel Rocky Mountain Clinical Research, LLC

Englewood, Colorado, 80113, United States

Location

Georgetown University; Research Division, Psychiatry

Washington D.C., District of Columbia, 20007, United States

Location

University of South Florida

Tampa, Florida, 33613, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

John Hopkins University School of Medicine

Baltimore, Maryland, 21287, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Dent Neurological Institute

Amherst, New York, 14226, United States

Location

Columbia University

New York, New York, 10032-3725, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

Location

The University of Texas Health Science Center at Houston; McGovern Medical School

Houston, Texas, 77030, United States

Location

University of Utah Clinical Neurosciences Center

Salt Lake City, Utah, 84132, United States

Location

Evergreen Health Care Center

Kirkland, Washington, 98034, United States

Location

Hospital Ramos Mejía

CABA, C1221ADC, Argentina

Location

INEBA

Capital Federal, C1192AAX, Argentina

Location

Hospital Britanico de Buenos Aires

Ciudad Autonoma Buenos Aires, C1284AEB, Argentina

Location

WESTMEAD HOSPITAL; Deparment of Neurology

Westmead, New South Wales, 2145, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Royal Melbourne Hospital; Department of Neurology

Parkville, Victoria, 3050, Australia

Location

Uniklinik fuer Neurologie, Medizinische Universitaet Innsbruck; Department fuer Neurologie

Innsbruck, 6020, Austria

Location

Christian-Doppler-Klinik - Universitätsklinikum; Universitätskliniik für Neurologie

Salzburg, 5020, Austria

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 1Z1, Canada

Location

University of British Columbia Hospital; Division of Neurology

Vancouver, British Columbia, V6T 2B5, Canada

Location

True North Clinical Research-Halifax

Halifax, Nova Scotia, B3S 1N2, Canada

Location

Centre for Movement Disorders

North YORK, Ontario, M3B 2S7, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1Y 4E9, Canada

Location

Centre Hospitalier de l?Université de Montréal (CHUM)

Montreal, Quebec, H2X 0C2, Canada

Location

Centro de Trastornos del Movimiento (CETRAM); CETRAM

Santiago, 9120000, Chile

Location

Aarhus Universitetshospital; Neurologisk Afdeling F, Neurogenetisk Afsnit

Aarhus N, 8200, Denmark

Location

Rigshospitalet, Hukommelsesklinikken

København Ø, 2100, Denmark

Location

CHU Angers, Batiement Larrey 2, Neurologie

Angers, 49933, France

Location

Hopital Henri Mondor; Service de Neurologie

Créteil, 94010, France

Location

Hopital Roger Salengro Service de Neurologie

Lille, France

Location

CHU de la Timone - Hopital d Adultes; Service de Neurologie

Marseille, 13005, France

Location

Hopital Gui de Chauliac; Neurologie

Montpellier, 34295, France

Location

Hôpital Pitié Salpêtrère; Département de Génétique et Cytogénétique

Paris, 75651, France

Location

CHU toulouse - Hôpital Purpan; Departement de Neurologie

Toulouse, 31059, France

Location

Uniklinik RWTH Aachen; Klinik für Neurologie

Aachen, 52074, Germany

Location

Charité - Universitätsmed. Berlin, Klinik für Psychiatrie und Psychotherapie; Abt. Neuropsychiatrie

Berlin, 10117, Germany

Location

St. Josef-Hospital, Neurologische Klinik der Ruhr-Uni; Huntington-Center NRW, Abt. Neurodegeneration

Bochum, 44791, Germany

Location

German Center for Neurodegenerative Diseases (DZNE)

Bonn, 53127, Germany

Location

Universitätsklinikum Erlangen, Abteilung Molekulare Neurologie

Erlangen, 91054, Germany

Location

Universitätsklinikum Schleswig-Holstein / Campus Lübeck; Zentrum für Seltene Erkrankungen

Lübeck, 23538, Germany

Location

George-Huntington- Institut GmbH; Technologiepark Münster

Münster, 48149, Germany

Location

Universitätsklinikum Ulm; Klinik für Neurologie

Ulm, 89081, Germany

Location

IRCCS Casa Sollievo Della Sofferenza; Unità Ricerca e Cura Huntington e Malattie Rare

San Giovanni Rotondo, Apulia, 71013, Italy

Location

IRCCS Istituto delle Scienze Neurologiche; UOC Clinica Neurologica

Bologna, Emilia-Romagna, 40139, Italy

Location

Azienda Ospedaliera Sant'Andrea; UOC Neurologia

Rome, Lazio, 00189, Italy

Location

Irccs A.O.U.San Martino Ist; Dinogmi

Genoa, Liguria, 16132, Italy

Location

Fondazione IRCCS Istituto Neurologico Carlo Besta; U.O.C. Genetica Medica-Neurogenetica

Milan, Lombardy, 20133, Italy

Location

A.O.U. Careggi; Diaprtimento Scienze Neurologiche e Psichiatriche

Florence, Tuscany, Italy

Location

Kuwana City Medical Center

Mie, 511-0061, Japan

Location

National Hospital Organization Niigata National Hospital

Niigata, 945-8585, Japan

Location

Okayama University Graduate School of Medicine, Densitry and Pharmaceutical Sciences.

Okayama, 700-8558, Japan

Location

Osaka General Medical Center

Osaka, 558-8558, Japan

Location

National Center of Neurology and Psychiatry

Tokyo, 187-8551, Japan

Location

Universitair Medisch Centrum Groningen

Groningen, 9713 GZ, Netherlands

Location

LUMC

Leiden, 2333 ZA, Netherlands

Location

Auckland DHB - Neurlogy Department; Neurology Department

Auckland, New Zealand

Location

New Zealand Brain Research Institute

Christchurch, 8011, New Zealand

Location

Wellington Hospital; Department of Neurology

Wellington, 6021, New Zealand

Location

Szpital Sw. Wojciecha; Oddzial Neurologiczny

Gdansk, 80-462, Poland

Location

Krakowska Akademia Neurologii Sp z o.o. Centrum Neurologii K

Krakow, 31-505, Poland

Location

Instytut Psychiatrii i Neurologii

Warsaw, 02-957, Poland

Location

FSBHI Siberian Clinical Center of the Federal Medical and Biological Agency

Krasnoyarsk, Krasnoyarsk Krai, 660037, Russia

Location

Research Center of Neurology; Neurology Department #5

Moskva, Moscow Oblast, 125367, Russia

Location

?linical hospital at Kazan station, Republican Center for Movement Disorders and Botulinum Therapy

Kazan', Tatarstan Republic, 420061, Russia

Location

Hospital de Cruces; Servicio de Neurologia

Barakaldo, Vizcaya, 48903, Spain

Location

Hospital Universitario de Badajoz; Servicio de Neurología

Badajoz, 06080, Spain

Location

Hospital Clinic Servicio de Neurologia

Barcelona, 08036, Spain

Location

Hospital de la Santa Creu i Sant Pau; Servicio de Neurologia

Barcelona, 08041, Spain

Location

Hospital Universitario de Burgos. Servicio de Neurología

Burgos, 09006, Spain

Location

Hospital Ramon y Cajal; Servicio de Neurologia

Madrid, 28034, Spain

Location

Fundacion Jimenez Diaz; Servicio de Neurología

Madrid, 28040, Spain

Location

Hospital Universitario Virgen Macarena; Servicio de Neurologia

Seville, 41009, Spain

Location

Hospital Universitario la Fe; Servicio de Neurologia

Valencia, 46026, Spain

Location

Universitätsspital Basel; Neurologie

Basel, 4031, Switzerland

Location

Neurozentrum Siloah

Gümligen, 3073, Switzerland

Location

Aberdeen Royal Infirmary; Medical Genectics

Aberdeen, AB25 2ZD, United Kingdom

Location

Queen Elizabeth Hospital

Birmingham, B15 2TH, United Kingdom

Location

Cambridge Centre for Brain Repair; Department of Clinical Nuerosciences, Addenbrookes Hospital

Cambridge, CB2 0SP, United Kingdom

Location

University Hospital of Wales; Division of Psychological Medicine and Clinical Neurosciences

Cardiff, CF14 4XW, United Kingdom

Location

Queen Elizabeth University Hospital Glasgow

Glasgow, G51 4TF, United Kingdom

Location

Leeds General Infirmary

Leeds, LS1 3EX, United Kingdom

Location

National Hospital For Neurology and Neurosurgery

London, WC1N 3BG, United Kingdom

Location

Central Manchester University Hospitals NHS Foundation Trust; Manchester Centre for Genomic Medicine

Manchester, M13 9WL, United Kingdom

Location

John Radcliffe Hospital

Oxford, OX3 9DU, United Kingdom

Location

Royal Hallamshire Hospital

Sheffield, S10 2JF, United Kingdom

Location

University Hospital Southampton NHS Foundation Trust

Southhampton, SO16 6YD, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 31381524 DERIVED

• 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.

  PMID: 30776019 DERIVED

MeSH Terms

Conditions

Chorea

Interventions

tominersen

Condition Hierarchy (Ancestors)

Dyskinesias; Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2018
• First Posted: December 3, 2018
• Study Start: January 23, 2019
• Primary Completion: March 24, 2022
• Study Completion: March 24, 2022
• Last Updated: March 1, 2024
• Results First Posted: November 7, 2023

Record last verified: 2024-02

Locations

AR (3); RU (3); DK (2); US (20); NZ (3); PL (3); AU (2); GB (11); FR (7); CH (2); CA (6); ES (9); CL (1); DE (8); JP (5); IT (6); NL (2)