Back to resultsA Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7234292 (ISIS 443139) in Huntington's Disease Patients Who Participated in Prior Investigational Studies of RO7234292 (ISIS 443139)
Primary Purpose
Huntington's Disease
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
RO7234292 (RG6042)
Sponsored by
About this trial
This is an interventional treatment trial for Huntington's Disease
Eligibility Criteria
Key Inclusion Criteria:
- Must have completed dosing in ISIS 443139-CS1
Key Exclusion Criteria:
- Any new condition or worsening of existing condition that could make the patient unsuitable for participation or interfere with the patient participating in and/or completing the study
Sites / Locations
- The University of British Columbia; The Centre for Huntington Disease
- Charité - Universitätsmedizin Berlin, Campus Charité Mitte; Klinik für Psychiatrie und Psychotherapi
- St. Josef and St. Elisabeth GmbH ; Klinikum Bochum, Zentralapotheke
- Universitaetsklinikum Ulm
- NIHR Welcome Trust Birmingham CRF - University Hospitals Birmingham; Department of Neuropsychiatry
- University of Cambridge - John van Geest Centre for Brain Repair
- Cardiff University School of Medicine; Institute of Psychological Medicine Clinical Neurosciences
- Leonard Wolfson Experimental Neurology Centre
- 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 Monthly
RO7234292 Bimonthly
Arm Description
RO7234292 is administered every 28 days intrathecally for 14 months.
RO7234292 is administered every 56 days intrathecally for 14 months following 2 monthly doses to serve as a loading dose.
Outcomes
Primary Outcome Measures
Percentage of Participants With Adverse Events
Adverse Events include Adverse Events that started at or after Date/Time of First Exposure to Treatment and procedure-related Adverse Events occurring before the start of treatment.
Secondary Outcome Measures
RO7234292 CSF Trough Concentrations by Study Day Prior to Monthly and Bimonthly IT Administration of 120 mg RO7234292 (Primary Analysis)
CSF mHTT Protein Concentration Logarithmic Value Change in Geometric Mean (95%CI) From Baseline
The results of the planned analysis related to mHTT protein levels in CSF are reported
Mean Percentage Change in Ventricular Volume Boundary Shift Integral From Baseline to 15 Months
Mean Percentage Change in Caudate Volume Boundary Shift Integral From Baseline to 15 Months
Mean Percentage Change in Whole Brain Volume Boundary Shift Integral From Baseline to 15 Months
EEG Parameters: Mean Change From Baseline to 15 Months in Absolute Power [8-12Hz]
Mean Change From Baseline in Huntington's Disease Cognitive Assessment Battery Composite Score
HD Cognitive Assessment Battery (HD-CAB) was developed to assess cognitive dysfunction in late premanifest and early manifest HD patients. HD-CAB combines scores from six cognitive tests: SDMT, Self-Paced Tapping, Emotional Recognition, CANTAB One Touch Stocking, Hopkins Verbal Learning Test - Revised, and Trail-Making Test. A multi-component score is derived by transforming the subject's score on each cognitive test to a z-score. Using z-scores permits the combination of test scores with different scales. Unlike other measures that use an external reference population to create z-scores, HD-CAB uses the baseline data of the study. Individually, for each of the six cognitive tests, the study baseline mean is subtracted from the subject's score, and this value is divided by the study baseline standard deviation. The six z-scores are averaged to produce the HD-CAB score. A positive change from baseline indicates improvement in cognitive function; a negative change indicates worsening.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03342053
Brief Title
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7234292 (ISIS 443139) in Huntington's Disease Patients Who Participated in Prior Investigational Studies of RO7234292 (ISIS 443139)
Official Title
An Open-Label Extension Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7234292 (ISIS 443139) in Huntington's Disease Patients Who Participated in Prior Investigational Studies of RO7234292 (ISIS 443139)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
January 2, 2018 (Actual)
Primary Completion Date
October 8, 2019 (Actual)
Study Completion Date
October 8, 2019 (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
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study will test the safety, tolerability, pharmacokinetics and pharmacodynamics of RO7234292 administered intrathecally to adult patients with Huntington's Disease.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Huntington's Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
46 (Actual)
8. Arms, Groups, and Interventions
Arm Title
RO7234292 Monthly
Arm Type
Experimental
Arm Description
RO7234292 is administered every 28 days intrathecally for 14 months.
Arm Title
RO7234292 Bimonthly
Arm Type
Experimental
Arm Description
RO7234292 is administered every 56 days intrathecally for 14 months following 2 monthly doses to serve as a loading dose.
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 Adverse Events
Description
Adverse Events include Adverse Events that started at or after Date/Time of First Exposure to Treatment and procedure-related Adverse Events occurring before the start of treatment.
Time Frame
From baseline up to 18 months
Secondary Outcome Measure Information:
Title
RO7234292 CSF Trough Concentrations by Study Day Prior to Monthly and Bimonthly IT Administration of 120 mg RO7234292 (Primary Analysis)
Time Frame
From baseline to Day 421
Title
CSF mHTT Protein Concentration Logarithmic Value Change in Geometric Mean (95%CI) From Baseline
Description
The results of the planned analysis related to mHTT protein levels in CSF are reported
Time Frame
From Baseline to Day 421
Title
Mean Percentage Change in Ventricular Volume Boundary Shift Integral From Baseline to 15 Months
Time Frame
Baseline up to 15 months
Title
Mean Percentage Change in Caudate Volume Boundary Shift Integral From Baseline to 15 Months
Time Frame
Baseline up to 15 months
Title
Mean Percentage Change in Whole Brain Volume Boundary Shift Integral From Baseline to 15 Months
Time Frame
Baseline up to 15 months
Title
EEG Parameters: Mean Change From Baseline to 15 Months in Absolute Power [8-12Hz]
Time Frame
Baseline to 15 Months
Title
Mean Change From Baseline in Huntington's Disease Cognitive Assessment Battery Composite Score
Description
HD Cognitive Assessment Battery (HD-CAB) was developed to assess cognitive dysfunction in late premanifest and early manifest HD patients. HD-CAB combines scores from six cognitive tests: SDMT, Self-Paced Tapping, Emotional Recognition, CANTAB One Touch Stocking, Hopkins Verbal Learning Test - Revised, and Trail-Making Test. A multi-component score is derived by transforming the subject's score on each cognitive test to a z-score. Using z-scores permits the combination of test scores with different scales. Unlike other measures that use an external reference population to create z-scores, HD-CAB uses the baseline data of the study. Individually, for each of the six cognitive tests, the study baseline mean is subtracted from the subject's score, and this value is divided by the study baseline standard deviation. The six z-scores are averaged to produce the HD-CAB score. A positive change from baseline indicates improvement in cognitive function; a negative change indicates worsening.
Time Frame
Baseline to 15 Months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Must have completed dosing in ISIS 443139-CS1
Key Exclusion Criteria:
Any new condition or worsening of existing condition that could make the patient unsuitable for participation or interfere with the patient participating in and/or completing the study
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
The University of British Columbia; The Centre for Huntington Disease
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6T 2B5
Country
Canada
Facility Name
Charité - Universitätsmedizin Berlin, Campus Charité Mitte; Klinik für Psychiatrie und Psychotherapi
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
St. Josef and St. Elisabeth GmbH ; Klinikum Bochum, Zentralapotheke
City
Bochum
ZIP/Postal Code
44791
Country
Germany
Facility Name
Universitaetsklinikum Ulm
City
Ulm
ZIP/Postal Code
89081
Country
Germany
Facility Name
NIHR Welcome Trust Birmingham CRF - University Hospitals Birmingham; Department of Neuropsychiatry
City
Birmingham
ZIP/Postal Code
B15 2FG
Country
United Kingdom
Facility Name
University of Cambridge - John van Geest Centre for Brain Repair
City
Cambridge
ZIP/Postal Code
CB2 0PY
Country
United Kingdom
Facility Name
Cardiff University School of Medicine; Institute of Psychological Medicine Clinical Neurosciences
City
Cardiff
ZIP/Postal Code
CF24 4HQ
Country
United Kingdom
Facility Name
Leonard Wolfson Experimental Neurology Centre
City
London
ZIP/Postal Code
WC1N 3BG
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
Learn more about this trial
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7234292 (ISIS 443139) in Huntington's Disease Patients Who Participated in Prior Investigational Studies of RO7234292 (ISIS 443139)
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