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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

Primary Purpose

Huntington Disease

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
RO7234292 (RG6042)
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Huntington Disease

Eligibility Criteria

25 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Uab Medicine
  • University of California San Diego
  • Stanford Univ Medical Center
  • SC3 Research Group, Inc
  • CenExel Rocky Mountain Clinical Research, LLC
  • Georgetown University; Research Division, Psychiatry
  • University of South Florida
  • Northwestern University
  • John Hopkins University School of Medicine
  • Dent Neurological Institute
  • Columbia University
  • University of Pittsburgh
  • Vanderbilt University Medical Center
  • The University of Texas Health Science Center at Houston; McGovern Medical School
  • Uniklinik fuer Neurologie, Medizinische Universitaet Innsbruck; Department fuer Neurologie
  • University of British Columbia Hospital; Division of Neurology
  • Centre for Movement Disorders
  • Ottawa Hospital Research Institute
  • Centre Hospitalier de l?Université de Montréal (CHUM)
  • Charité - Universitätsmed. Berlin, Klinik für Psychiatrie und Psychotherapie; Abt. Neuropsychiatrie
  • St. Josef-Hospital, Neurologische Klinik der Ruhr-Uni; Huntington-Center NRW, Abt. Neurodegeneration
  • Universitätsklinikum Ulm; Klinik für Neurologie
  • Fondazione IRCCS Istituto Neurologico Carlo Besta; U.O.C. Genetica Medica-Neurogenetica
  • IRCCS Casa Sollievo Della Sofferenza; Unità Ricerca e Cura Huntington e Malattie Rare
  • Universitair Medisch Centrum Groningen
  • LUMC
  • Hospital Universitario de Badajoz; Servicio de Neurología
  • Hospital Clinic Servicio de Neurologia
  • Hospital de la Santa Creu i Sant Pau; Servicio de Neurologia
  • Hospital Universitario de Burgos. Servicio de Neurología
  • Hospital Ramon y Cajal; Servicio de Neurologia
  • Fundacion Jimenez Diaz; Servicio de Neurología
  • Hospital Universitario Virgen Macarena; Servicio de Neurologia
  • Birmingham and Solihull Mental Health Foundation Trust; Institute of Clinical Sciences
  • Cambridge Centre for Brain Repair; Department of Clinical Nuerosciences, Addenbrookes Hospital
  • University Hospital of Wales; Division of Psychological Medicine and Clinical Neurosciences
  • University College London Hospitals NHS Foundation Trust - University College Hospital
  • Central Manchester University Hospitals NHS Foundation Trust; Manchester Centre for Genomic Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

RO7234292 (RG6042) Q8W

RO7234292 (RG6042) Q16W

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.
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.
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.

Secondary Outcome Measures

Full Information

First Posted
February 11, 2019
Last Updated
August 9, 2023
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT03842969
Brief Title
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

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
April 23, 2019 (Actual)
Primary Completion Date
March 25, 2022 (Actual)
Study Completion Date
March 30, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Huntington Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
236 (Actual)

8. Arms, Groups, and Interventions

Arm Title
RO7234292 (RG6042) Q8W
Arm Type
Experimental
Arm Description
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.
Arm Title
RO7234292 (RG6042) Q16W
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
RO7234292 (RG6042)
Other Intervention Name(s)
Tominersen
Intervention Description
Intrathecal injection
Primary Outcome Measure Information:
Title
Percentage of Participants With Treatment Emergent Adverse Events
Description
The reported are the treatment-emergent AEs with an onset date up to 5 months after last study drug intake.
Time Frame
Up to Approximately 3 Years
Title
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)
Description
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.
Time Frame
Up to approximately 3 Years
Title
Change From Baseline in Cognition, Using Montreal Cognitive Assessment (MoCA)
Description
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.
Time Frame
Up to Approximately 3 Years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Uab Medicine
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
University of California San Diego
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
Stanford Univ Medical Center
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
SC3 Research Group, Inc
City
Pasadena
State/Province
California
ZIP/Postal Code
91105
Country
United States
Facility Name
CenExel Rocky Mountain Clinical Research, LLC
City
Englewood
State/Province
Colorado
ZIP/Postal Code
80113
Country
United States
Facility Name
Georgetown University; Research Division, Psychiatry
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
University of South Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33613
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
John Hopkins University School of Medicine
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Dent Neurological Institute
City
Amherst
State/Province
New York
ZIP/Postal Code
14226
Country
United States
Facility Name
Columbia University
City
New York
State/Province
New York
ZIP/Postal Code
10032-3725
Country
United States
Facility Name
University of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37212
Country
United States
Facility Name
The University of Texas Health Science Center at Houston; McGovern Medical School
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Uniklinik fuer Neurologie, Medizinische Universitaet Innsbruck; Department fuer Neurologie
City
Innsbruck
ZIP/Postal Code
6020
Country
Austria
Facility Name
University of British Columbia Hospital; Division of Neurology
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6T 2B5
Country
Canada
Facility Name
Centre for Movement Disorders
City
North York
State/Province
Ontario
ZIP/Postal Code
M3B 2S7
Country
Canada
Facility Name
Ottawa Hospital Research Institute
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1Y 4E9
Country
Canada
Facility Name
Centre Hospitalier de l?Université de Montréal (CHUM)
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2X 0C2
Country
Canada
Facility Name
Charité - Universitätsmed. Berlin, Klinik für Psychiatrie und Psychotherapie; Abt. Neuropsychiatrie
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
St. Josef-Hospital, Neurologische Klinik der Ruhr-Uni; Huntington-Center NRW, Abt. Neurodegeneration
City
Bochum
ZIP/Postal Code
44791
Country
Germany
Facility Name
Universitätsklinikum Ulm; Klinik für Neurologie
City
Ulm
ZIP/Postal Code
89081
Country
Germany
Facility Name
Fondazione IRCCS Istituto Neurologico Carlo Besta; U.O.C. Genetica Medica-Neurogenetica
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20133
Country
Italy
Facility Name
IRCCS Casa Sollievo Della Sofferenza; Unità Ricerca e Cura Huntington e Malattie Rare
City
San Giovanni Rotondo (FG)
State/Province
Puglia
ZIP/Postal Code
71013
Country
Italy
Facility Name
Universitair Medisch Centrum Groningen
City
Groningen
ZIP/Postal Code
9713 GZ
Country
Netherlands
Facility Name
LUMC
City
Leiden
ZIP/Postal Code
2333 ZA
Country
Netherlands
Facility Name
Hospital Universitario de Badajoz; Servicio de Neurología
City
Badajoz
ZIP/Postal Code
06080
Country
Spain
Facility Name
Hospital Clinic Servicio de Neurologia
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hospital de la Santa Creu i Sant Pau; Servicio de Neurologia
City
Barcelona
ZIP/Postal Code
08041
Country
Spain
Facility Name
Hospital Universitario de Burgos. Servicio de Neurología
City
Burgos
ZIP/Postal Code
09006
Country
Spain
Facility Name
Hospital Ramon y Cajal; Servicio de Neurologia
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Fundacion Jimenez Diaz; Servicio de Neurología
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Hospital Universitario Virgen Macarena; Servicio de Neurologia
City
Sevilla
ZIP/Postal Code
41009
Country
Spain
Facility Name
Birmingham and Solihull Mental Health Foundation Trust; Institute of Clinical Sciences
City
Birmingham
ZIP/Postal Code
B15 2TT
Country
United Kingdom
Facility Name
Cambridge Centre for Brain Repair; Department of Clinical Nuerosciences, Addenbrookes Hospital
City
Cambridge
ZIP/Postal Code
CB2 0SP
Country
United Kingdom
Facility Name
University Hospital of Wales; Division of Psychological Medicine and Clinical Neurosciences
City
Cardiff
ZIP/Postal Code
CF14 4XW
Country
United Kingdom
Facility Name
University College London Hospitals NHS Foundation Trust - University College Hospital
City
London
ZIP/Postal Code
NW1 2PG
Country
United Kingdom
Facility Name
Central Manchester University Hospitals NHS Foundation Trust; Manchester Centre for Genomic Medicine
City
Manchester
ZIP/Postal Code
M13 9WL
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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).

Learn more about this trial

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

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