Trial in Adult Subjects With Spinocerebellar Ataxia

Phase 2

Completed

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

Interventions: Drug: Placebo
Drug: Troriluzole

Registration Number: NCT02960893

Lead Sponsor: Biohaven Pharmaceuticals, Inc.

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 141

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	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.
Placebo	Troriluzole	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.
Troriluzole	Troriluzole	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.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Total Score on the Scale for the Assessment and Rating of Ataxia (SARA) at Randomization Phase Week 8	Baseline, 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.

Secondary Outcome Measures

Name	Time	Method
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)	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.	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.
Number of Participants With Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Treatment-Emergent AEs (TEAEs) During the Randomization Phase	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).	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.
Number of Participants With Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Treatment Emergent AEs (TEAEs) During the Extension Phase	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).	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.
Number of Participants With Impression of Benefit Via Use of the Patient Global Impression of Change (PGI-C) Index Scale During Randomization Phase	Randomization Phase Week 8	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.

Trial Locations

Locations (18): Emory University
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Atlanta, Georgia, United States
University of Texas Southwestern
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Dallas, Texas, United States
Northwestern University
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Chicago, Illinois, United States
University of Chicago
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Chicago, Illinois, United States
University of Florida
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Gainesville, Florida, United States
University of California, Los Angeles
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Los Angeles, California, United States
St. Joseph's Hospital and Medical Center
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Phoenix, Arizona, United States
University of California, San Francisco
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San Francisco, California, United States
Harvard University (Massachusetts General Hospital)
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Boston, Massachusetts, United States
Harvard University (Beth Israel Deaconess Medical Center)
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Boston, Massachusetts, United States
Houston Methodist Research Center
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Houston, Texas, United States
University of Rochester Medical Center
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Rochester, New York, United States
University of Colorado Denver
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Denver, Colorado, United States
Johns Hopkins University
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Baltimore, Maryland, United States
University of Michigan
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Ann Arbor, Michigan, United States
Columbia University
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New York, New York, United States
CNS Trial
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Long Beach, California, United States
University of South Florida
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Tampa, Florida, United States