The primary purpose of this study was to compare the efficacy of BHV-4157 (Troriluzole) 140 milligrams (mg) once daily versus placebo after 8 weeks of treatment in participants with spinocerebellar ataxia (SCA).
The study was conducted in 2 phases: Randomization Phase (8 weeks) followed by an open-label Extension Phase (336 weeks). During the Randomization Phase, participants received either Troriluzole 140 mg or matching placebo up to 8 weeks. Participants who agreed to enter the Open-label Extension Phase continued dosing of Troriluzole 140 mg for 336 weeks. The study was subsequently amended to follow participants for a total of 336 weeks in the Open-label Extension Phase.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
141
Randomization Phase: Neat (i.e., drug substance without excipients); loose filled capsule.
Drug: Placebo Randomization Phase: Matching placebo loose filled capsule.
OLE phase: Neat capsule or formulated capsule (i.e., drug substance with excipients).
St. Joseph's Hospital and Medical Center
Phoenix, Arizona, United States
CNS Trial
Long Beach, California, United States
University of California, Los Angeles
Los Angeles, California, United States
University of California, San Francisco
San Francisco, California, United States
University of Colorado Denver
Denver, Colorado, United States
University of Florida
Gainesville, Florida, United States
University of South Florida
Tampa, Florida, United States
Emory University
Atlanta, Georgia, United States
Northwestern University
Chicago, Illinois, United States
University of Chicago
Chicago, Illinois, United States
...and 8 more locations
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.
Time frame: Baseline, Randomization Phase Week 8
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 participant 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.
Time frame: From first dose of study drug to 30 days post the last dose in the Randomization Phase (Up to 12 weeks)
Number of Participants With Deaths, SAEs, AEs Leading to Discontinuation and TEAEs During the OLE 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 participant 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.
Time frame: From first dose of study drug to 30 days post the last dose in the OLE Phase (Up to 340 weeks)
Number of Participants Who Received At Least One Dose of Troriluzole in the Randomization Phase or OLE Phase With Deaths, SAEs, AEs Leading to Discontinuation and 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 participant 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.
Time frame: From first dose of study drug to 30 days post the last dose in the OLE Phase (Up to 348 weeks after last randomization participant was enrolled)
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.
Time frame: Randomization Phase Week 8
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