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)

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)

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

Study Overview

• Status: Completed
• Conditions: Huntington's Disease
• Intervention / Treatment: Drug: RO7234292 (RG6042)

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6T 2B5
      • The University of British Columbia; The Centre for Huntington Disease
• Germany
  • Berlin, Germany, 10117
    • Charité - Universitätsmedizin Berlin, Campus Charité Mitte; Klinik für Psychiatrie und Psychotherapi
  • Bochum, Germany, 44791
    • St. Josef and St. Elisabeth GmbH ; Klinikum Bochum, Zentralapotheke
  • Ulm, Germany, 89081
    • Universitaetsklinikum Ulm
• United Kingdom
  • Birmingham, United Kingdom, B15 2FG
    • NIHR Welcome Trust Birmingham CRF - University Hospitals Birmingham; Department of Neuropsychiatry
  • Cambridge, United Kingdom, CB2 0PY
    • University of Cambridge - John van Geest Centre for Brain Repair
  • Cardiff, United Kingdom, CF24 4HQ
    • Cardiff University School of Medicine; Institute of Psychological Medicine Clinical Neurosciences
  • London, United Kingdom, WC1N 3BG
    • Leonard Wolfson Experimental Neurology Centre
  • Manchester, United Kingdom, M13 9WL
    • Central Manchester University Hospitals NHS Foundation Trust; Manchester Centre for Genomic Medicine

Participation Criteria

Eligibility Criteria

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

Description

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

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 Monthly; RO7234292 is administered every 28 days intrathecally for 14 months.	Drug: RO7234292 (RG6042); Intrathecal injection; Other Names: Tominersen
Experimental: RO7234292 Bimonthly; RO7234292 is administered every 56 days intrathecally for 14 months following 2 monthly doses to serve as a loading dose.	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 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.	From baseline up to 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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	From Baseline to Day 421
Mean Percentage Change in Ventricular Volume Boundary Shift Integral From Baseline to 15 Months		Baseline up to 15 months
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
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	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.	Baseline to 15 Months

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2018
• Primary Completion (Actual): October 8, 2019
• Study Completion (Actual): October 8, 2019

Study Registration Dates

• First Submitted: October 31, 2017
• First Submitted That Met QC Criteria: November 13, 2017
• First Posted (Actual): November 14, 2017

Study Record Updates

• Last Update Posted (Actual): March 24, 2022
• Last Update Submitted That Met QC Criteria: March 1, 2022
• Last Verified: March 1, 2022

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: BN40697

Drug and device information, study documents

• 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