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

An Open-Label Extension Study to Evaluate the Long-Term Safety and Tolerability of Intrathecally Administered RO7234292 (RG6042) in Patients With Huntington's Disease

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.

Study Overview

• Status: Completed
• Conditions: Huntington Disease
• Intervention / Treatment: Drug: RO7234292 (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.

• Study Type: Interventional
• Enrollment (Actual): 236
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • Uniklinik fuer Neurologie, Medizinische Universitaet Innsbruck; Department fuer Neurologie
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6T 2B5
      • University of British Columbia Hospital; Division of Neurology
  • Ontario
    • North York, Ontario, Canada, M3B 2S7
      • Centre for Movement Disorders
    • Ottawa, Ontario, Canada, K1Y 4E9
      • Ottawa Hospital Research Institute
  • Quebec
    • Montreal, Quebec, Canada, H2X 0C2
      • Centre Hospitalier de l?Université de Montréal (CHUM)
• Germany
  • Berlin, Germany, 10117
    • Charité - Universitätsmed. Berlin, Klinik für Psychiatrie und Psychotherapie; Abt. Neuropsychiatrie
  • Bochum, Germany, 44791
    • St. Josef-Hospital, Neurologische Klinik der Ruhr-Uni; Huntington-Center NRW, Abt. Neurodegeneration
  • Ulm, Germany, 89081
    • Universitätsklinikum Ulm; Klinik für Neurologie
• Italy
  • Lombardia
    • Milano, Lombardia, Italy, 20133
      • Fondazione IRCCS Istituto Neurologico Carlo Besta; U.O.C. Genetica Medica-Neurogenetica
  • Puglia
    • San Giovanni Rotondo (FG), Puglia, Italy, 71013
      • IRCCS Casa Sollievo Della Sofferenza; Unità Ricerca e Cura Huntington e Malattie Rare
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Universitair Medisch Centrum Groningen
  • Leiden, Netherlands, 2333 ZA
    • LUMC
• Spain
  • Badajoz, Spain, 06080
    • Hospital Universitario de Badajoz; Servicio de Neurología
  • Barcelona, Spain, 08041
    • Hospital de la Santa Creu i Sant Pau; Servicio de Neurologia
  • Barcelona, Spain, 08036
    • Hospital Clinic Servicio de Neurologia
  • Burgos, Spain, 09006
    • Hospital Universitario de Burgos. Servicio de Neurología
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal; Servicio de Neurologia
  • Madrid, Spain, 28040
    • Fundacion Jimenez Diaz; Servicio de Neurología
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena; Servicio de Neurologia
• United Kingdom
  • Birmingham, United Kingdom, B15 2TT
    • Birmingham and Solihull Mental Health Foundation Trust; Institute of Clinical Sciences
  • Cambridge, United Kingdom, CB2 0SP
    • Cambridge Centre for Brain Repair; Department of Clinical Nuerosciences, Addenbrookes Hospital
  • Cardiff, United Kingdom, CF14 4XW
    • University Hospital of Wales; Division of Psychological Medicine and Clinical Neurosciences
  • London, United Kingdom, NW1 2PG
    • University College London Hospitals NHS Foundation Trust - University College Hospital
  • Manchester, United Kingdom, M13 9WL
    • Central Manchester University Hospitals NHS Foundation Trust; Manchester Centre for Genomic Medicine
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Uab Medicine
  • California
    • La Jolla, California, United States, 92093
      • University of California San Diego
    • Palo Alto, California, United States, 94304
      • Stanford Univ Medical Center
    • Pasadena, California, United States, 91105
      • SC3 Research Group, Inc
  • Colorado
    • Englewood, Colorado, United States, 80113
      • CenExel Rocky Mountain Clinical Research, LLC
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University; Research Division, Psychiatry
  • Florida
    • Tampa, Florida, United States, 33613
      • University of South Florida
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • John Hopkins University School of Medicine
  • New York
    • Amherst, New York, United States, 14226
      • Dent Neurological Institute
    • New York, New York, United States, 10032-3725
      • Columbia University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center at Houston; McGovern Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RO7234292 (RG6042) Q8W; 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.	Drug: RO7234292 (RG6042); Intrathecal injection; Other Names: Tominersen
Experimental: RO7234292 (RG6042) Q16W; 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.	Drug: RO7234292 (RG6042); Intrathecal injection; Other Names: Tominersen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2019
• Primary Completion (Actual): March 25, 2022
• Study Completion (Actual): March 30, 2022

Study Registration Dates

• First Submitted: February 11, 2019
• First Submitted That Met QC Criteria: February 14, 2019
• First Posted (Actual): February 15, 2019

Study Record Updates

• Last Update Posted (Actual): August 31, 2023
• Last Update Submitted That Met QC Criteria: August 9, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Dyskinesias; Heredodegenerative Disorders, Nervous System; Dementia; Cognition Disorders; Chorea; Huntington Disease
• Other Study ID Numbers: BN40955; 2018-003898-94 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No