An Open-Label Extension Study to Evaluate Long-Term Safety and Tolerability of RO7234292 (RG6042) in Huntington's Disease Participants Who Participated in Prior Roche and Genentech Sponsored Studies

Phase 3

Completed

Conditions: Huntington Disease

Interventions: Drug: RO7234292 (RG6042)

Registration Number: NCT03842969

Lead Sponsor: Hoffmann-La Roche

Brief Summary: This study will evaluate the long-term safety and tolerability of RO7234292 (RG6042) in participants who have completed other F. Hoffmann-La Roche, Ltd.-sponsored and/or Genentech-sponsored studies in the Huntington's disease (HD) in the development program for RG6042.

Detailed Description: Entry into the study should occur at the time the participant completes participation in one of the preceding studies. Upon completion of the inclusion visit, eligible participants will receive either RO7234292 (RG6042) every 8 weeks (Q8W) or RO7234292 (RG6042) every 16 weeks (Q16W) by the bolus intrathecal injection.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 236

Inclusion Criteria

Prior enrollment in a Roche-sponsored or Genentech-sponsored study in HD for the RO7234292 (RG6042) development program that made provision for entry into an OLE study
For women of childbearing potential: agreement to remain abstinent or use contraceptive measures
For men: agreement to remain abstinent or use a condom, and agreement to refrain from donating sperm
Patients who were screened and eligible for the placebo-controlled Phase III Study BN40423 but could not be randomized prior to the close of Study BN40423 enrollment due to challenges relating to the COVID-19 pandemic

Inclusion criteria of patients who were screened and eligible for the placebo-controlled Phase III Study BN40423 but could not be randomized prior to the close of Study BN40423 enrollment due to challenges relating to the COVID-19 pandemic:

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

Withdrawal of consent from the preceding study
Permanent discontinuation of RO7234292 (RG6042) for any drug-related safety concern during the preceding study or meeting of any study treatment discontinuation criteria specified in the preceding study at the time of enrollment into this study
An ongoing, unresolved, clinically significant medical problem that in the judgment of the investigator would make it unsafe for the patient to participate in this study
Antiplatelet or anticoagulant therapy within 14 days prior to inclusion or anticipated use during the study, including, but not limited to, aspirin, clopidogrel, dipyridamole, warfarin, dabigatran, rivaroxaban, and apixaban
History of bleeding diathesis or coagulopathy
Platelet count less than the lower limit of normal
Concurrent participation in any therapeutic clinical trial
Study treatment (RO7234292/RG6042) is commercially marketed in the patient's country for the patient-specific disease and is accessible to the patient
Pregnant or breastfeeding, or intending to become pregnant during the study or within 5 months after the final dose of study drug

Exclusion criteria of patients who were screened and eligible for the placebo-controlled Phase III Study BN40423 but could not be randomized prior to the close of Study BN40423 enrollment due to challenges relation to the COVID-19 pandemic:

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
RO7234292 (RG6042) Q8W	RO7234292 (RG6042)	Participants who received open-label RO7234292 Q4W in a preceding study or who received RO7234292 Q4W in this study may be randomly allocated to receive RO7234292 Q8W. Participants who previously received open-label of RO7234292 Q8W in a preceding study or are currently receiving RO7234292 Q8W in this study will receive RO7234292 Q8W. Participants who previously received placebo, or did not previously receive treatment with RO7234292 or received short-term treatment with a treatment-free follow-up period may be randomly allocated to receive RO7234292 Q8W. Participants who previously received blinded placebo Q8W may receive RO7234292 Q8W. Participants who received blinded RO7234292 Q8W will receive open-label RO7234929 Q8W. Participants who received blinded placebo Q8W may receive RO7234292 Q8W. Participants who received blinded RO7234292 Q4W or blinded placebo Q4W may be randomly allocated to receive open-label of RO7234292 Q8W.
RO7234292 (RG6042) Q16W	RO7234292 (RG6042)	Participants who previously received open-label RO7234292 Q4W in a preceding study or who received RO7234292 Q4W in this study may be randomly allocated to receive RO7234292 Q16W. Participants who previously received placebo in a preceding study or did not previously receive treatment with RO7234292 or received short-term treatment with a treatment-free follow-up period may be randomly allocated to receive RO7234292 Q16W. Participants who previously received blinded placebo Q8W will receive RO7234292 Q8W. Participants who previously received blinded RO7234292 Q16W will receive open-label RO7234292 Q16W. Participants who received blinded RO7234292 Q4W or blinded placebo Q4W may be randomly allocated to receive open-label of RO7234292 Q16W. Participants who previously received open-label RO7234292 Q16W will receive open-label RO7234292 Q16W.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Treatment Emergent Adverse Events	Up to Approximately 3 Years	The reported are the treatment-emergent AEs with an onset date up to 5 months after last study drug intake.
Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia Suicide Severity Rating Scale (C-SSRS)	Up to approximately 3 Years	C-SSRS is to assess suicidal ideation and behavior. 4 constructs measured: severity of ideation, intensity of ideation, behavior, and lethality of actual suicide attempts. Yes/No data collected for 10 categories, composite endpoints based on the categories are followed over time to monitor safety. Composite endpoint of suicidal ideation (1-5), n and (%) are the number and % of who experience any of the five suicidal ideation events at least once after receiving the first dose of study medication. Composite endpoint of suicidal behavior (6-10), n and (%) are the number and percent of patients who experience any 1of 5 suicidal behavior events at least 1 after receiving the 5 dose of study medication. Composite endpoint of suicidal ideation or behavior (1-10), n and (%) are the number and % of patients who experience any 1 the 10 suicidal ideation or behavior events at least once after receiving the first dose of study medication.
Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA)	Up to Approximately 3 Years	MoCA contains a series of basic assessments, including attention and visuospatial tasks. The total score ranges from 0-30, where lower scores indicate greater impairment. MOCA01-Total scores are reported. The data presented are absolute scores for baseline and change from baseline for post-baseline assessments. All Arms except Tominersen 120mg Q4W (Period 1) belong to the Milestone Period 2.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (38): Hospital de la Santa Creu i Sant Pau; Servicio de Neurologia
🇪🇸
Barcelona, Spain
University of Pittsburgh
🇺🇸
Pittsburgh, Pennsylvania, United States
CenExel Rocky Mountain Clinical Research, LLC
🇺🇸
Englewood, Colorado, United States
Northwestern University
🇺🇸
Chicago, Illinois, United States
Uab Medicine
🇺🇸
Birmingham, Alabama, United States
SC3 Research Group, Inc
🇺🇸
Pasadena, California, United States
Stanford Univ Medical Center
🇺🇸
Palo Alto, California, United States
John Hopkins University School of Medicine
🇺🇸
Baltimore, Maryland, United States
University of California San Diego
🇺🇸
La Jolla, California, United States
Uniklinik fuer Neurologie, Medizinische Universitaet Innsbruck; Department fuer Neurologie
🇦🇹
Innsbruck, Austria
Centre Hospitalier de l?Université de Montréal (CHUM)
🇨🇦
Montreal, Quebec, Canada
Universitair Medisch Centrum Groningen
🇳🇱
Groningen, Netherlands
University of South Florida
🇺🇸
Tampa, Florida, United States
Columbia University
🇺🇸
New York, New York, United States
Centre for Movement Disorders
🇨🇦
North York, Ontario, Canada
Dent Neurological Institute
🇺🇸
Amherst, New York, United States
Charité - Universitätsmed. Berlin, Klinik für Psychiatrie und Psychotherapie; Abt. Neuropsychiatrie
🇩🇪
Berlin, Germany
The University of Texas Health Science Center at Houston; McGovern Medical School
🇺🇸
Houston, Texas, United States
Vanderbilt University Medical Center
🇺🇸
Nashville, Tennessee, United States
Ottawa Hospital Research Institute
🇨🇦
Ottawa, Ontario, Canada
Universitätsklinikum Ulm; Klinik für Neurologie
🇩🇪
Ulm, Germany
Fondazione IRCCS Istituto Neurologico Carlo Besta; U.O.C. Genetica Medica-Neurogenetica
🇮🇹
Milano, Lombardia, Italy
St. Josef-Hospital, Neurologische Klinik der Ruhr-Uni; Huntington-Center NRW, Abt. Neurodegeneration
🇩🇪
Bochum, Germany
IRCCS Casa Sollievo Della Sofferenza; Unità Ricerca e Cura Huntington e Malattie Rare
🇮🇹
San Giovanni Rotondo (FG), Puglia, Italy
Hospital Universitario de Badajoz; Servicio de Neurología
🇪🇸
Badajoz, Spain
LUMC
🇳🇱
Leiden, Netherlands
Hospital Clinic Servicio de Neurologia
🇪🇸
Barcelona, Spain
University Hospital of Wales; Division of Psychological Medicine and Clinical Neurosciences
🇬🇧
Cardiff, United Kingdom
Hospital Universitario de Burgos. Servicio de Neurología
🇪🇸
Burgos, Spain
Hospital Universitario Virgen Macarena; Servicio de Neurologia
🇪🇸
Sevilla, Spain
Birmingham and Solihull Mental Health Foundation Trust; Institute of Clinical Sciences
🇬🇧
Birmingham, United Kingdom
Hospital Ramon y Cajal; Servicio de Neurologia
🇪🇸
Madrid, Spain
Fundacion Jimenez Diaz; Servicio de Neurología
🇪🇸
Madrid, Spain
Cambridge Centre for Brain Repair; Department of Clinical Nuerosciences, Addenbrookes Hospital
🇬🇧
Cambridge, United Kingdom
University College London Hospitals NHS Foundation Trust - University College Hospital
🇬🇧
London, United Kingdom
Central Manchester University Hospitals NHS Foundation Trust; Manchester Centre for Genomic Medicine
🇬🇧
Manchester, United Kingdom
Georgetown University; Research Division, Psychiatry
🇺🇸
Washington, District of Columbia, United States
University of British Columbia Hospital; Division of Neurology
🇨🇦
Vancouver, British Columbia, Canada