Clinical trial NCT03842969: 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
Official title: An Open-Label Extension Study to Evaluate the Long-Term Safety and Tolerability of Intrathecally Administered RO7234292 (RG6042) in Patients With Huntington's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Huntington Disease
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2019-02-15
Enrollment: 236
Sex: ALL
Minimum age (years): 25
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With Treatment Emergent Adverse Events
timeFrame: Up to Approximately 3 Years
measure: 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)
timeFrame: Up to approximately 3 Years
measure: Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA)
timeFrame: Up to Approximately 3 Years
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Uab Medicine
state: Alabama
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: 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: 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: Innsbruck
country: Austria
facility: Uniklinik fuer Neurologie, Medizinische Universitaet Innsbruck; Department fuer Neurologie
city: Vancouver
country: Canada
facility: University of British Columbia Hospital; Division of Neurology
state: British Columbia
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: 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: Ulm
country: Germany
facility: Universitätsklinikum Ulm; Klinik für Neurologie
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Neurologico Carlo Besta; U.O.C. Genetica Medica-Neurogenetica
state: Lombardia
city: San Giovanni Rotondo (FG)
country: Italy
facility: IRCCS Casa Sollievo Della Sofferenza; Unità Ricerca e Cura Huntington e Malattie Rare
state: Puglia
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Leiden
country: Netherlands
facility: LUMC
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: Birmingham
country: United Kingdom
facility: Birmingham and Solihull Mental Health Foundation Trust; Institute of Clinical Sciences
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: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust - University College Hospital
city: Manchester
country: United Kingdom
facility: Central Manchester University Hospitals NHS Foundation Trust; Manchester Centre for Genomic Medicine
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: