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)

• ClinicalTrials.gov Identifier: NCT03342053
• Recruitment Status: Completed
• First Posted: November 14, 2017
• Results First Posted: January 19, 2021
• Last Update Posted: January 19, 2021
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

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.

Condition or disease	Intervention/treatment	Phase
Huntington's Disease	Drug: RO7234292 (RG6042)	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: January 2, 2018
• Actual Primary Completion Date: October 8, 2019
• Actual Study Completion Date: October 8, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: RO7234292 Monthly; RO7234292 is administered every 28 days intrathecally for 14 months.	Drug: RO7234292 (RG6042); Intrathecal injection; Other Name: 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 Name: Tominersen

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Adverse Events [ Time Frame: 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 :

1. 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 ]
2. CSF mHTT Protein Concentration [ Time Frame: Baseline up to 15 months ]
   Data on mHTT protein levels in CSF were not available at the time of writing as validation of the mHTT assay in a regulated environment was ongoing and sample analysis was pending successful validation of the assay. results of the planned analysis related to mHTT protein levels in CSF will be reported once available
3. Mean Percentage Change in Ventricular Volume Boundary Shift Integral From Baseline to 15 Months [ Time Frame: Baseline up to 15 months ]
4. Mean Percentage Change in Caudate Volume Boundary Shift Integral From Baseline to 15 Months [ Time Frame: Baseline up to 15 months ]
5. Mean Percentage Change in Whole Brain Volume Boundary Shift Integral From Baseline to 15 Months [ Time Frame: Baseline up to 15 months ]
6. EEG Parameters: Mean Change From Baseline to 15 Months in Absolute Power [8-12Hz] [ Time Frame: Baseline to 15 Months ]
7. Mean Change From Baseline in Huntington's Disease Cognitive Assessment Battery Composite Score [ Time Frame: 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.

Eligibility Criteria

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

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

Contacts and Locations

Locations

Canada, British Columbia

The University of British Columbia; The Centre for Huntington Disease

Vancouver, British Columbia, Canada, V6T 2B5

Germany

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

Berlin, Germany, 10117

St. Josef and St. Elisabeth GmbH ; Klinikum Bochum, Zentralapotheke

Bochum, Germany, 44791

Universitaetsklinikum Ulm

Ulm, Germany, 89081

United Kingdom

NIHR Welcome Trust Birmingham CRF - University Hospitals Birmingham; Department of Neuropsychiatry

Birmingham, United Kingdom, B15 2FG

University of Cambridge - John van Geest Centre for Brain Repair

Cambridge, United Kingdom, CB2 0PY

Cardiff University School of Medicine; Institute of Psychological Medicine Clinical Neurosciences

Cardiff, United Kingdom, CF24 4HQ

Leonard Wolfson Experimental Neurology Centre

London, United Kingdom, WC1N 3BG

Central Manchester University Hospitals NHS Foundation Trust; Manchester Centre for Genomic Medicine

Manchester, United Kingdom, M13 9WL

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

  Study Documents (Full-Text)

Documents provided by Hoffmann-La Roche:

Study Protocol and Statistical Analysis Plan  [PDF] August 30, 2018

More Information

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT03342053
• Other Study ID Numbers: BN40697
• First Posted: November 14, 2017
• Results First Posted: January 19, 2021
• Last Update Posted: January 19, 2021
• Last Verified: January 2021

• 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

Additional relevant MeSH terms:

Huntington Disease; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Chorea; Dyskinesias; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Cognition Disorders; Neurocognitive Disorders; Mental Disorders