Clinical trial NCT03761849: A Study to Evaluate the Efficacy and Safety of Intrathecally Administered RO7234292 (RG6042) in Participants With Manifest Huntington's Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Huntingtons Disease
Keywords: HD, RG6042, intrathecal, ASO, antisense oligonucleotide
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2018-12-03
Enrollment: 899
Sex: ALL
Minimum age (years): 25
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)


Eligibility 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

Primary outcomes:
measure: Change From Baseline in the Composite Unified Huntington's Disease Rating Scale (cUHDRS) Score-Z Score
timeFrame: Weeks 21 for ODC and 69 for NDC
measure: Change From Baseline in the Total Functional Capacity (TFC) Score
timeFrame: Weeks 21 for ODC and 69 for NDC
Secondary outcomes:
measure: Change From Baseline in Total Motor Score (TMS)
timeFrame: Weeks 21 for ODC and 69 for NDC
measure: Change From Baseline in Symbol Digit Modalities Test (SDMT) Scores' Least Squares Mean Values
timeFrame: Weeks 21 for ODC and 69 NDC
measure: Change From Baseline in Stroop Word Reading (SWR) Test Scores' Least Squares Mean Values
timeFrame: Weeks 21 for ODC and 69 for NDC
measure: Change From Baseline in the Clinical Global Impression, Severity Scale (CGI-S) Scores' Least Squares Mean Values
timeFrame: Week 69 for NDC Only
measure: Percentage of Patients With a Decrease From Baseline of >=1 Point on the Total Functional Capacity (TFC) Score
timeFrame: Week 69 for NDC only
measure: Percentage of Patients With a Decline From Baseline of >=1.2 Points on the Composite Unified Huntington's Disease Rating Scale-cUHDRS Score
timeFrame: Week 69 for NDC Only
measure: Percentage of Patients With an Unchanged or Improved Score on the Clinical Global Impression, Change Scale Score
timeFrame: Weeks 53 and 69 NDC only
measure: Percentage of Participants With Adverse Events
timeFrame: Up to 117 Weeks (29 months)
measure: Change From Baseline in Montreal Cognitive Assessment (MoCA)
timeFrame: Up to Week 21 for ODC, Up to Week 69 for NDC
measure: Percentage of Participants With Suicidal Ideation or Behavior, as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score
timeFrame: For ODC at 13th Month, for NDC at Week 101
measure: Concentration of RO7234292 in Plasma
timeFrame: Week 21 for ODC and Week 69 for NDC
measure: Trough Concentration of RO7234292 in Cerebrospinal Fluid (CSF)
timeFrame: Week 21 for ODC and Week 69 for NDC
measure: Incidence of Anti-Drug Antibodies (ADAs).
timeFrame: Week 21 for ODC and Week 69 for NDC
measure: Titer and Antibody Subtype, Determined if ADAs Are Identified
timeFrame: Week 21 for ODC and Week 69 for NDC
measure: Change From Baseline in CSF mHTT Protein Level
timeFrame: Baseline, Week 101
measure: Change From Baseline in Whole and Regional Brain Volumes, as Detrmined by Structural Magnetic Resonance Imaging (MRI)
timeFrame: Week 13 for ODC
measure: Change From Baseline in CSF Neurofilament Light Chain (NfL) Proteint Level
timeFrame: Week 21 for ODC, Weeks 21 and 69 for NDC
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Uab Medicine
state: Alabama
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Palo Alto
country: United States
facility: Stanford Univ Medical Center
state: California
city: Pasadena
country: United States
facility: SC3 Research Group, Inc
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical System
state: California
city: Englewood
country: United States
facility: CenExel Rocky Mountain Clinical Research, LLC
state: Colorado
city: Washington
country: United States
facility: Georgetown University; Research Division, Psychiatry
state: District of Columbia
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Baltimore
country: United States
facility: John Hopkins University School of Medicine
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Amherst
country: United States
facility: Dent Neurological Institute
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston; McGovern Medical School
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Clinical Neurosciences Center
state: Utah
city: Kirkland
country: United States
facility: Evergreen Health Care Center
state: Washington
city: Caba
country: Argentina
facility: Hospital Ramos Mejía
city: Capital Federal
country: Argentina
facility: INEBA
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Hospital Britanico de Buenos Aires
city: Westmead
country: Australia
facility: WESTMEAD HOSPITAL; Deparment of Neurology
state: New South Wales
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital; Department of Neurology
state: Victoria
city: Innsbruck
country: Austria
facility: Uniklinik fuer Neurologie, Medizinische Universitaet Innsbruck; Department fuer Neurologie
city: Salzburg
country: Austria
facility: Christian-Doppler-Klinik - Universitätsklinikum; Universitätskliniik für Neurologie
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Vancouver
country: Canada
facility: University of British Columbia Hospital; Division of Neurology
state: British Columbia
city: Halifax
country: Canada
facility: True North Clinical Research-Halifax
state: Nova Scotia
city: North York
country: Canada
facility: Centre for Movement Disorders
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute
state: Ontario
city: Montreal
country: Canada
facility: Centre Hospitalier de l?Université de Montréal (CHUM)
state: Quebec
city: Santiago
country: Chile
facility: Centro de Trastornos del Movimiento (CETRAM); CETRAM
city: Aarhus N
country: Denmark
facility: Aarhus Universitetshospital; Neurologisk Afdeling F, Neurogenetisk Afsnit
city: København Ø
country: Denmark
facility: Rigshospitalet, Hukommelsesklinikken
city: Angers Cedex 9
country: France
facility: CHU Angers, Batiement Larrey 2, Neurologie
city: Creteil
country: France
facility: Hopital Henri Mondor; Service de Neurologie
city: Lille
country: France
facility: Hopital Roger Salengro Service de Neurologie
city: Marseille
country: France
facility: CHU de la Timone - Hopital d Adultes; Service de Neurologie
city: Montpellier
country: France
facility: Hopital Gui de Chauliac; Neurologie
city: Paris
country: France
facility: Hôpital Pitié Salpêtrère; Département de Génétique et Cytogénétique
city: Toulouse
country: France
facility: CHU toulouse - Hôpital Purpan; Departement de Neurologie
city: Aachen
country: Germany
facility: Uniklinik RWTH Aachen; Klinik für Neurologie
city: Berlin
country: Germany
facility: Charité - Universitätsmed. Berlin, Klinik für Psychiatrie und Psychotherapie; Abt. Neuropsychiatrie
city: Bochum
country: Germany
facility: St. Josef-Hospital, Neurologische Klinik der Ruhr-Uni; Huntington-Center NRW, Abt. Neurodegeneration
city: Bonn
country: Germany
facility: German Center for Neurodegenerative Diseases (DZNE)
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen, Abteilung Molekulare Neurologie
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein / Campus Lübeck; Zentrum für Seltene Erkrankungen
city: Münster
country: Germany
facility: George-Huntington- Institut GmbH; Technologiepark Münster
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm; Klinik für Neurologie
city: Bologna
country: Italy
facility: IRCCS Istituto delle Scienze Neurologiche; UOC Clinica Neurologica
state: Emilia-Romagna
city: Roma
country: Italy
facility: Azienda Ospedaliera Sant'Andrea; UOC Neurologia
state: Lazio
city: Genova
country: Italy
facility: Irccs A.O.U.San Martino Ist; Dinogmi
state: Liguria
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Neurologico Carlo Besta; U.O.C. Genetica Medica-Neurogenetica
state: Lombardia
city: San Giovanni Rotondo
country: Italy
facility: IRCCS Casa Sollievo Della Sofferenza; Unità Ricerca e Cura Huntington e Malattie Rare
state: Puglia
city: Firenze
country: Italy
facility: A.O.U. Careggi; Diaprtimento Scienze Neurologiche e Psichiatriche
state: Toscana
city: Mie
country: Japan
facility: Kuwana City Medical Center
city: Niigata
country: Japan
facility: National Hospital Organization Niigata National Hospital
city: Okayama
country: Japan
facility: Okayama University Graduate School of Medicine, Densitry and Pharmaceutical Sciences.
city: Osaka
country: Japan
facility: Osaka General Medical Center
city: Tokyo
country: Japan
facility: National Center of Neurology and Psychiatry
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Leiden
country: Netherlands
facility: LUMC
city: Auckland
country: New Zealand
facility: Auckland DHB - Neurlogy Department; Neurology Department
city: Christchurch
country: New Zealand
facility: New Zealand Brain Research Institute
city: Wellington
country: New Zealand
facility: Wellington Hospital; Department of Neurology
city: Gdansk
country: Poland
facility: Szpital Sw. Wojciecha; Oddzial Neurologiczny
city: Krakow
country: Poland
facility: Krakowska Akademia Neurologii Sp z o.o. Centrum Neurologii K
city: Warszawa
country: Poland
facility: Instytut Psychiatrii i Neurologii
city: Krasnoyarsk
country: Russian Federation
facility: FSBHI Siberian Clinical Center of the Federal Medical and Biological Agency
state: Krasnojarsk
city: Moskva
country: Russian Federation
facility: Research Center of Neurology; Neurology Department #5
state: Moskovskaja Oblast
city: Kazan
country: Russian Federation
facility: ?linical hospital at Kazan station, Republican Center for Movement Disorders and Botulinum Therapy
state: Tatarstan
city: Barakaldo
country: Spain
facility: Hospital de Cruces; Servicio de Neurologia
state: Vizcaya
city: Badajoz
country: Spain
facility: Hospital Universitario de Badajoz; Servicio de Neurología
city: Barcelona
country: Spain
facility: Hospital Clinic Servicio de Neurologia
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau; Servicio de Neurologia
city: Burgos
country: Spain
facility: Hospital Universitario de Burgos. Servicio de Neurología
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal; Servicio de Neurologia
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz; Servicio de Neurología
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena; Servicio de Neurologia
city: Valencia
country: Spain
facility: Hospital Universitario la Fe; Servicio de Neurologia
city: Basel
country: Switzerland
facility: Universitätsspital Basel; Neurologie
city: Gümligen
country: Switzerland
facility: Neurozentrum Siloah
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary; Medical Genectics
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Cambridge
country: United Kingdom
facility: Cambridge Centre for Brain Repair; Department of Clinical Nuerosciences, Addenbrookes Hospital
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales; Division of Psychological Medicine and Clinical Neurosciences
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital Glasgow
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
city: London
country: United Kingdom
facility: National Hospital For Neurology and Neurosurgery
city: Manchester
country: United Kingdom
facility: Central Manchester University Hospitals NHS Foundation Trust; Manchester Centre for Genomic Medicine
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
city: Southhampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.