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

NCT03842969 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: BN409552018-003898-94
• Study Type: interventional
• Target: 236
• Locations: 8 countries
• Sites: 38

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.

Conditions

Huntington Disease

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (2)

RO7234292 (RG6042) Q8W

EXPERIMENTAL

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)

RO7234292 (RG6042) Q16W

EXPERIMENTAL

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)

Interventions

RO7234292 (RG6042) DRUG

Intrathecal injection

Also known as: Tominersen

RO7234292 (RG6042) Q16W; RO7234292 (RG6042) Q8W

Eligibility Criteria

• Age: 25 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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).

You may not qualify if:

• 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
• 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
• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (38)

Uab Medicine

Birmingham, Alabama, 35294, United States

Location

University of California San Diego

La Jolla, California, 92093, United States

Location

Stanford Univ Medical Center

Palo Alto, California, 94304, United States

Location

SC3 Research Group, Inc

Pasadena, California, 91105, United States

Location

CenExel Rocky Mountain Clinical Research, LLC

Englewood, Colorado, 80113, United States

Location

Georgetown University; Research Division, Psychiatry

Washington D.C., District of Columbia, 20007, United States

Location

University of South Florida

Tampa, Florida, 33613, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

John Hopkins University School of Medicine

Baltimore, Maryland, 21287, United States

Location

Dent Neurological Institute

Amherst, New York, 14226, United States

Location

Columbia University

New York, New York, 10032-3725, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

Location

The University of Texas Health Science Center at Houston; McGovern Medical School

Houston, Texas, 77030, United States

Location

Uniklinik fuer Neurologie, Medizinische Universitaet Innsbruck; Department fuer Neurologie

Innsbruck, 6020, Austria

Location

University of British Columbia Hospital; Division of Neurology

Vancouver, British Columbia, V6T 2B5, Canada

Location

Centre for Movement Disorders

North YORK, Ontario, M3B 2S7, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1Y 4E9, Canada

Location

Centre Hospitalier de l?Université de Montréal (CHUM)

Montreal, Quebec, H2X 0C2, Canada

Location

Charité - Universitätsmed. Berlin, Klinik für Psychiatrie und Psychotherapie; Abt. Neuropsychiatrie

Berlin, 10117, Germany

Location

St. Josef-Hospital, Neurologische Klinik der Ruhr-Uni; Huntington-Center NRW, Abt. Neurodegeneration

Bochum, 44791, Germany

Location

Universitätsklinikum Ulm; Klinik für Neurologie

Ulm, 89081, Germany

Location

IRCCS Casa Sollievo Della Sofferenza; Unità Ricerca e Cura Huntington e Malattie Rare

San Giovanni Rotondo (FG), Apulia, 71013, Italy

Location

Fondazione IRCCS Istituto Neurologico Carlo Besta; U.O.C. Genetica Medica-Neurogenetica

Milan, Lombardy, 20133, Italy

Location

Universitair Medisch Centrum Groningen

Groningen, 9713 GZ, Netherlands

Location

LUMC

Leiden, 2333 ZA, Netherlands

Location

Hospital Universitario de Badajoz; Servicio de Neurología

Badajoz, 06080, Spain

Location

Hospital Clinic Servicio de Neurologia

Barcelona, 08036, Spain

Location

Hospital de la Santa Creu i Sant Pau; Servicio de Neurologia

Barcelona, 08041, Spain

Location

Hospital Universitario de Burgos. Servicio de Neurología

Burgos, 09006, Spain

Location

Hospital Ramon y Cajal; Servicio de Neurologia

Madrid, 28034, Spain

Location

Fundacion Jimenez Diaz; Servicio de Neurología

Madrid, 28040, Spain

Location

Hospital Universitario Virgen Macarena; Servicio de Neurologia

Seville, 41009, Spain

Location

Birmingham and Solihull Mental Health Foundation Trust; Institute of Clinical Sciences

Birmingham, B15 2TT, United Kingdom

Location

Cambridge Centre for Brain Repair; Department of Clinical Nuerosciences, Addenbrookes Hospital

Cambridge, CB2 0SP, United Kingdom

Location

University Hospital of Wales; Division of Psychological Medicine and Clinical Neurosciences

Cardiff, CF14 4XW, United Kingdom

Location

University College London Hospitals NHS Foundation Trust - University College Hospital

London, NW1 2PG, United Kingdom

Location

Central Manchester University Hospitals NHS Foundation Trust; Manchester Centre for Genomic Medicine

Manchester, M13 9WL, United Kingdom

Location

MeSH Terms

Conditions

Huntington Disease

Interventions

tominersen

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Chorea; Dyskinesias; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2019
• First Posted: February 15, 2019
• Study Start: April 23, 2019
• Primary Completion: March 25, 2022
• Study Completion: March 30, 2022
• Last Updated: August 31, 2023
• Results First Posted: August 31, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share

Locations

US (14); IT (2); ES (7); NL (2); AU (1); GB (5); CA (4); DE (3)