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)

Huntington's Disease Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03342053
• Other study ID #: BN40697
• Status: Completed
• Phase: Phase 2
• Start date: January 2, 2018
• Est. completion date: October 8, 2019

Study information

• Verified date: March 2022
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: October 8, 2019
• Est. primary completion date: October 8, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Huntington Disease
• Huntington's Disease

Intervention

Drug:
• RO7234292 (RG6042)
Intrathecal injection

Locations

Country	Name	City	State
Canada	The University of British Columbia; The Centre for Huntington Disease	Vancouver	British Columbia
Germany	Charité - Universitätsmedizin Berlin, Campus Charité Mitte; Klinik für Psychiatrie und Psychotherapi	Berlin
Germany	St. Josef and St. Elisabeth GmbH ; Klinikum Bochum, Zentralapotheke	Bochum
Germany	Universitaetsklinikum Ulm	Ulm
United Kingdom	NIHR Welcome Trust Birmingham CRF - University Hospitals Birmingham; Department of Neuropsychiatry	Birmingham
United Kingdom	University of Cambridge - John van Geest Centre for Brain Repair	Cambridge
United Kingdom	Cardiff University School of Medicine; Institute of Psychological Medicine Clinical Neurosciences	Cardiff
United Kingdom	Leonard Wolfson Experimental Neurology Centre	London
United Kingdom	Central Manchester University Hospitals NHS Foundation Trust; Manchester Centre for Genomic Medicine	Manchester

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Canada,  Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Mean Percentage Change in Ventricular Volume Boundary Shift Integral From Baseline to 15 Months		Baseline up to 15 months
Secondary	Mean Percentage Change in Caudate Volume Boundary Shift Integral From Baseline to 15 Months		Baseline up to 15 months
Secondary	Mean Percentage Change in Whole Brain Volume Boundary Shift Integral From Baseline to 15 Months		Baseline up to 15 months
Secondary	EEG Parameters: Mean Change From Baseline to 15 Months in Absolute Power [8-12Hz]		Baseline to 15 Months
Secondary	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