Troriluzole in Adult Subjects With Spinocerebellar Ataxia

Study Overview
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Brief Summary
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The purpose of this study is to compare the efficacy of Troriluzole (200mg once daily) versus placebo after 48 weeks of treatment in subjects with spinocerebellar ataxia (SCA).

Official Title
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A Phase III, Long-Term, Randomized, Double-blind, Placebo-controlled Trial of Troriluzole in Adult Subjects With Spinocerebellar Ataxia.

Conditions
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Spinocerebellar Ataxias, Spinocerebellar Ataxia Type 1, Spinocerebellar Ataxia Type 2, Spinocerebellar Ataxia Type 3, Spinocerebellar Ataxia Type 6, Spinocerebellar Ataxia Type 7, Spinocerebellar Ataxia Type 8, Spinocerebellar Ataxia Type 10

Intervention / Treatment
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* Drug: troriluzole
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with a known or suspected diagnosis of the following specific hereditary ataxias: SCA1, SCA2, SCA3, SCA6, SCA7, SCA8 and SCA10; currently only enrolling SCA 1, SCA2, SCA3, SCA7, and SCA10 (the cap has been met for SCA6 and SCA8 (on May 31, 2019)); A subject should have a confirmed genotypic diagnosis from a CLIA certified lab (can produce test results); or, A subject has a family member that has a confirmed genotypic diagnosis from a CLIA certified lab (can produce test results) and must be willing to undergo genetic testing to confirm underlying SCA diagnosis; or, A subject has a confirmed genotypic diagnosis from a lab that is not CLIA certified and must be willing to undergo genetic testing to confirm underlying SCA diagnosis; or, A subject has clinical evidence that supports diagnosis of one of the aforementioned SCA genotypes but does not have producible test results from a CLIA certified lab from either a family member or for his or herself and the subject must be willing to undergo such testing to confirm the SCA diagnosis (in this case, site must wait for results of genotypic testing prior to randomization) Ability to ambulate 8 meters without human assistance (canes and other devices allowed) Screening f-SARA total score ≥3; Score of ≥1 on gait subsection of the f-SARA Determined by the investigator to be medically stable at Baseline/randomization as assessed by medical history, physical examination, laboratory test results, and electrocardiogram testing. Exclusion Criteria: A ≥ 2-point difference on the Modified Functional SARA score between screening and baseline MMSE score <24 Any medical condition other than one of the hereditary ataxias specified in the inclusion criteria that could predominantly explain or contribute significantly to the subjects' symptoms of ataxia. A prominent spasticity or dystonia that, in the opinion of the investigator, will compromise the ability of the SARA instrument to assess underlying ataxia severity. A score of 4 on any individual item (Items 1-4) of the f-SARA Subjects should be excluded at screening or baseline if medical conditions have arisen or there is a change in disease status that could confound the ability of the SARA to accurately reflect changes in ataxia severity. Active liver disease or a history of hepatic intolerance to medications that in the investigator's judgment, is medically significant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: BHV-4157<br>Troriluzole 200mg by mouth | Drug: troriluzole<br>* 200 mg by mouth<br>|
| Placebo Comparator: Arm 2: Placebo<br>Placebo 200mg by mouth | Drug: Placebos<br>* 200 mg by mouth<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in the total score of the Modified Functional Scale for the Assessment and Rating of Ataxia (f-SARA) after 48 weeks of treatment. | An increase in the total score indicates a worsening of symptoms. | Baseline to week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1. Change from baseline in Patient Impression of Function and Activities of Daily Living Scale (PIFAS) score at Randomization Phase Week 48 | An increase in the total score indicates a worsening of symptoms. | Baseline to week 48 | 
| Change from baseline in Activities of Daily Living Scale from the Friedreich's Ataxia Rating Scale (FARS-ADL) at Randomization Week 48. | An increase in the total score indicates a worsening of symptoms. | Baseline to week 48 | 
| Change from baseline in Functional Staging for Ataxia from the Friedreich's Ataxia Rating Scale (FARS-FUNC) at Randomization Phase Week 48 | An increase in the total score indicates a worsening of symptoms. | Baseline to week 48 | 
| 4. Frequency of subjects with the following adverse events (AEs) identified from case report forms: AEs (by severity; by relationship to study drug; overall); SAEs; and AEs leading to treatment discontinuation. |  | Baseline to week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ataxia, SCA, Spinocerebellar Ataxia