Trial in Adult Participants With Spinocerebellar Ataxia (SCA)

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

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).

Study Overview

• Status: Completed
• Conditions: 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: Drug: Troriluzole; Drug: Placebo; Drug: Troriluzole

Detailed Description

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
• Enrollment (Actual): 141
• Phase: Phase 2; Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • St. Joseph's Hospital and Medical Center
  • California
    • Long Beach, California, United States, 90806
      • CNS Trial
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles
    • San Francisco, California, United States, 94158
      • University of California, San Francisco
  • Colorado
    • Denver, Colorado, United States, 80045
      • University of Colorado Denver
  • Florida
    • Gainesville, Florida, United States, 32611
      • University of Florida
    • Tampa, Florida, United States, 33612
      • University of South Florida
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Harvard University (Massachusetts General Hospital)
    • Boston, Massachusetts, United States, 02215
      • Harvard University (Beth Israel Deaconess Medical Center)
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • University of Michigan
  • New York
    • New York, New York, United States, 10032
      • Columbia University
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern
    • Houston, Texas, United States, 77030
      • Houston Methodist Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Participants 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 participants 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Troriluzole - Randomization Phase; Troriluzole - Randomization Phase: Participants received Troriluzole 140 mg capsules orally once daily (QD) for 8 weeks.	Drug: Troriluzole; Randomization Phase: Neat (i.e., drug substance without excipients); loose filled capsule.; Drug: Troriluzole; OLE phase: Neat capsule or formulated capsule (i.e., drug substance with excipients).
Placebo Comparator: Placebo - Randomization Phase; Placebo - Randomization Phase: Participants received matching placebo capsules orally QD for 8 weeks.	Drug: Placebo; Drug: Placebo Randomization Phase: Matching placebo loose filled capsule.
Experimental: Troriluzole/Troriluzole - OLE (Open Label Extension) Phase; Participants received Troriluzole 140 mg capsules orally QD for 48 weeks in the extension period and were allowed to participate in 288 weeks for expanded extension phase, for a total of 336 weeks of open-label treatment.	Drug: Troriluzole; Randomization Phase: Neat (i.e., drug substance without excipients); loose filled capsule.; Drug: Troriluzole; OLE phase: Neat capsule or formulated capsule (i.e., drug substance with excipients).
Experimental: Placebo/Troriluzole - OLE Phase; Participants who received placebo during randomization phase, received Troriluzole 140 mg capsules orally QD for 48 weeks in the extension period and were allowed to participate in 288 weeks for expanded extension phase, for a total of 336 weeks of open-label treatment.	Drug: Troriluzole; Randomization Phase: Neat (i.e., drug substance without excipients); loose filled capsule.; Drug: Placebo; Drug: Placebo Randomization Phase: Matching placebo loose filled capsule.; Drug: Troriluzole; OLE phase: Neat capsule or formulated capsule (i.e., drug substance with excipients).

What is the study measuring?

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 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
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.	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.	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.	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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Randomization Baseline in Total Score on the SARA at Extension Phase Week 48	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.	Randomization Baseline, Extension Phase Week 48

Collaborators and Investigators

• Sponsor: Biohaven Pharmaceuticals, Inc.

Publications and helpful links

General Publications

• Schmahmann JD, Pierce S, MacMore J, L'Italien GJ. Development and Validation of a Patient-Reported Outcome Measure of Ataxia. Mov Disord. 2021 Oct;36(10):2367-2377. doi: 10.1002/mds.28670. Epub 2021 Jun 11.

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2016
• Primary Completion (Actual): August 18, 2017
• Study Completion (Actual): September 20, 2024

Study Registration Dates

• First Submitted: November 4, 2016
• First Submitted That Met QC Criteria: November 8, 2016
• First Posted (Estimated): November 10, 2016

Study Record Updates

• Last Update Posted (Estimated): October 8, 2025
• Last Update Submitted That Met QC Criteria: September 19, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Spinocerebellar Ataxia; SCA
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Spinal Cord Diseases; Dyskinesias; Cerebellar Diseases; Cerebellar Ataxia; Spinocerebellar Degenerations; Ataxia; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Spinocerebellar Ataxias
• Other Study ID Numbers: BHV4157-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No