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)

Phase 2

Completed

• Conditions: Huntington's Disease
• Interventions: Drug: RO7234292 (RG6042)

• Registration Number: NCT03342053
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

This study will test the safety, tolerability, pharmacokinetics and pharmacodynamics of RO7234292 administered intrathecally to adult patients with Huntington's Disease.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2017-10-31
• Study First Submitted QC: 2017-11-13
• Study First Posted: 2017-11-14
• Study Start: 2018-01-02
• Primary Completion: 2019-10-08
• Study Completion: 2019-10-08
• Results First Submitted: 2020-10-07
• Results First Submitted QC: 2021-01-15
• Results First Posted: 2021-01-19
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-01
• Last Update Posted: 2022-03-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 46

Inclusion Criteria

• Must have completed dosing in ISIS 443139-CS1

Key

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
RO7234292 Monthly	RO7234292 (RG6042)	RO7234292 is administered every 28 days intrathecally for 14 months.
RO7234292 Bimonthly	RO7234292 (RG6042)	RO7234292 is administered every 56 days intrathecally for 14 months following 2 monthly doses to serve as a loading dose.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Adverse Events	From baseline up to 18 months	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

Name	Time	Method
RO7234292 CSF Trough Concentrations by Study Day Prior to Monthly and Bimonthly IT Administration of 120 mg RO7234292 (Primary Analysis)	From baseline to Day 421
Mean Percentage Change in Caudate Volume Boundary Shift Integral From Baseline to 15 Months	Baseline up to 15 months
Mean Percentage Change in Whole Brain Volume Boundary Shift Integral From Baseline to 15 Months	Baseline up to 15 months
CSF mHTT Protein Concentration Logarithmic Value Change in Geometric Mean (95%CI) From Baseline	From Baseline to Day 421	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	Baseline up to 15 months
EEG Parameters: Mean Change From Baseline to 15 Months in Absolute Power [8-12Hz]	Baseline to 15 Months
Mean Change From Baseline in Huntington's Disease Cognitive Assessment Battery Composite Score	Baseline to 15 Months	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.

Trial Locations

Locations (9)

Central Manchester University Hospitals NHS Foundation Trust; Manchester Centre for Genomic Medicine; 🇬🇧 Manchester, United Kingdom

Leonard Wolfson Experimental Neurology Centre; 🇬🇧 London, United Kingdom

Universitaetsklinikum Ulm; 🇩🇪 Ulm, Germany

University of Cambridge - John van Geest Centre for Brain Repair; 🇬🇧 Cambridge, United Kingdom

Charité - Universitätsmedizin Berlin, Campus Charité Mitte; Klinik für Psychiatrie und Psychotherapi; 🇩🇪 Berlin, Germany

The University of British Columbia; The Centre for Huntington Disease; 🇨🇦 Vancouver, British Columbia, Canada

NIHR Welcome Trust Birmingham CRF - University Hospitals Birmingham; Department of Neuropsychiatry; 🇬🇧 Birmingham, United Kingdom

Cardiff University School of Medicine; Institute of Psychological Medicine Clinical Neurosciences; 🇬🇧 Cardiff, United Kingdom

St. Josef and St. Elisabeth GmbH ; Klinikum Bochum, Zentralapotheke; 🇩🇪 Bochum, Germany