Trial in Adult Subjects With Spinocerebellar Ataxia

Study Overview
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Brief Summary
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The primary purpose of this study is to compare the efficacy of BHV-4157 (Troriluzole) 140 milligrams (mg) once daily versus placebo after 8 weeks of treatment in subjects with spinocerebellar ataxia (SCA).

Detailed Description
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The study was conducted in 2 phases: Randomization Phase (8 weeks) followed by an open-label Extension Phase (48 weeks). During the Randomization Phase, participants received either Troriluzole 140 mg or matching placebo up to 8 weeks. Participants who agreed to enter the Extension Phase continued dosing of Troriluzole 140 mg for 48 weeks. The study was subsequently amended to follow participants for a total of 192 weeks in the Extension Phase.

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

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

Intervention / Treatment
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* Drug: Troriluzole
* Drug: Placebo
* Drug: Troriluzole


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Subjects with a known or suspected diagnosis of the following specific hereditary ataxias: SCA1, SCA2, SCA3, SCA6, SCA7, SCA8 and SCA10 Ability to ambulate 8 meters without assistance (canes and other devices allowed) Screening total Scale for the Assessment and Rating of Ataxia (SARA) score ≥8 Score of ≥ 2 on the gait subsection of the SARA Determined by the investigator to be medically stable at baseline/randomization and must be physically able and expected to complete the trial as designed Key Exclusion Criteria: 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 Mini Mental State Exam (MMSE) score < 24 SARA total score of > 30 points at screening Clinical history of stroke 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Troriluzole<br>Troriluzole - Randomization Phase: Participants received Troriluzole 140 mg capsules orally once daily (QD) for 8 weeks. Troriluzole/Troriluzole - Extension Phase: Participants received Troriluzole 140 mg capsules orally QD for 48 weeks. | Drug: Troriluzole<br>* Randomization Phase: Neat (i.e., drug substance without excipients); loose filled capsule.<br>Drug: Troriluzole<br>* Extension phase: Neat capsule or formulated capsule (i.e., drug substance with excipients).<br>|
| Placebo Comparator: Placebo<br>Placebo - Randomization Phase: Participants received matching placebo capsules orally QD for 8 weeks. Placebo/Troriluzole - Extension Phase: Participants who received placebo during randomization phase, received Troriluzole 140 mg capsules orally QD for 48 weeks. | Drug: Placebo<br>* Drug: Placebo Randomization Phase: Matching placebo loose filled capsule.<br>Drug: Troriluzole<br>* Extension phase: Neat capsule or formulated capsule (i.e., drug substance with excipients).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total Score on the Scale for the Assessment and Rating of Ataxia (SARA) at Randomization Phase Week 8 | The severity of ataxia was assessed with the SARA, an 8-item clinical rating scale from 0 (no ataxia) to 40 (most severe ataxia). The total score was derived as the sum of the individual items, which included gait (0-8), stance (0-6), sitting (0-4), speech disturbance (0-6), finger chase (0-4), nose-finger test (0-4), fast alternating hand movements (0-4), and heel-shin slide (0-4). Since the finger chase, nose-finger test, fast alternating hand movements, and heel-shin slide were repeated on both the right and left side, the average of the right and left side assessments was used to derive the total score. A negative change in score shows improvement. | Baseline, Randomization Phase Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Treatment-Emergent AEs (TEAEs) During the Randomization Phase | An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition, unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not related to study drug. An SAE was defined as an event which was fatal or life threatening, required or prolonged hospitalization, was significantly or permanently disabling or incapacitating, constituted a congenital anomaly or a birth defect, or suspected transmission of an infectious agent, or encompassed any other clinically significant event that could jeopardize the subject or require medical or surgical intervention to prevent one of the aforementioned outcomes. TEAEs were defined as those AEs that developed, worsened, or became serious after the first dose of study drug. | AEs from first dose of study drug to 2 weeks after the last dose (up to 10 weeks). SAEs from signing of informed consent form (ICF) to the start of the Extension (Ext) Phase or 30 days after the last dose (up to 12 weeks). | 
| Number of Participants With Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Treatment Emergent AEs (TEAEs) During the Extension Phase | An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition, unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not related to study drug. An SAE was defined as an event which was fatal or life threatening, required or prolonged hospitalization, was significantly or permanently disabling or incapacitating, constituted a congenital anomaly or a birth defect, or suspected transmission of an infectious agent, or encompassed any other clinically significant event that could jeopardize the subject or require medical or surgical intervention to prevent one of the aforementioned outcomes. TEAEs were defined as those AEs that developed, worsened, or became serious after the first dose of study drug. | AEs from first dose Ext Phase troriluzole to 2 weeks after last dose (up to 50 weeks after last subject enrolled in Ext Phase). SAEs from signing of ICF to 30 days after last dose (up to 52 weeks after last subject enrolled in Ext Phase). | 
| Number of Participants Who Received at Least One Dose of Troriluzole in the Randomization Phase or Extension Phase With Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Treatment Emergent AEs (TEAEs) | An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition, unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not related to study drug. An SAE was defined as an event which was fatal or life threatening, required or prolonged hospitalization, was significantly or permanently disabling or incapacitating, constituted a congenital anomaly or a birth defect, or suspected transmission of an infectious agent, or encompassed any other clinically significant event that could jeopardize the subject or require medical or surgical intervention to prevent one of the aforementioned outcomes. TEAEs were defined as those AEs that developed, worsened, or became serious after the first dose of study drug. | AEs from first dose of troriluzole to 2 weeks after last dose (up to 50 weeks after last Ext subject enrolled or up to 58 weeks after last Randomization [Rand] subject enrolled). SAEs from signing of ICF to 30 days after the last dose of troriluzole. | 
| Number of Participants With Impression of Benefit Via Use of the Patient Global Impression of Change (PGI-C) Index Scale During Randomization Phase | PGI-C is a patient self-reported global index scale that was used to rate the response of a condition to therapy. Participants rated their impression of benefit based on the following 7 categories: No change (or condition has gotten worse); Almost the same, hardly any change at all; A little better, but no noticeable change; Somewhat better, but the change has not made any real difference; Moderately better, and a slight but noticeable change; Better and a definitive improvement that has made a real and worthwhile difference; A great deal better and a considerable improvement that has made all the difference. | Randomization Phase Week 8 | 

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