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)

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

Official Title
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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)

Conditions
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Huntington's Disease

Intervention / Treatment
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* Drug: RO7234292 (RG6042)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RO7234292 Monthly<br>RO7234292 is administered every 28 days intrathecally for 14 months. | Drug: RO7234292 (RG6042)<br>* Intrathecal injection<br>* Other names: Tominersen;|
| Experimental: RO7234292 Bimonthly<br>RO7234292 is administered every 56 days intrathecally for 14 months following 2 monthly doses to serve as a loading dose. | Drug: RO7234292 (RG6042)<br>* Intrathecal injection<br>* Other names: Tominersen;|

What is the study measuring?
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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 |