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

Huntington Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03842969
• Other study ID #: BN40955
• Secondary ID: 2018-003898-94
• Status: Completed
• Phase: Phase 3
• Start date: April 23, 2019
• Est. completion date: March 30, 2022

Study information

• Verified date: August 2023
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 236
• Est. completion date: March 30, 2022
• Est. primary completion date: March 25, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Huntington Disease

Intervention

Drug:
• RO7234292 (RG6042)
Intrathecal injection

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Austria,  Canada,  Germany,  Italy,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Treatment Emergent Adverse Events	The reported are the treatment-emergent AEs with an onset date up to 5 months after last study drug intake.	Up to Approximately 3 Years
Primary	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)	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.	Up to approximately 3 Years
Primary	Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA)	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.	Up to Approximately 3 Years