Real-World Data Study of Troriluzole-Treated Patients With Spinocerebellar Ataxia (SCA) Compared to a Matched Natural History Control

Real-World Data Study Assessing the Efficacy of Troriluzole-Treated Subjects With Spinocerebellar Ataxia (SCA) Compared to a Matched External SCA Control Using Natural History Cohort Data

The purpose of this study is to leverage two sources of real-world data (RWD) to assess the effectiveness of troriluzole after three years of treatment in patients with SCA by comparison to an external control of untreated patients who were followed in a natural history cohort.

Real world evidence of effectiveness will be assessed from the RWD sources to examine the treatment effects of toriluzole in SCA out to 3 years. Progression rates of SCA differ by genotype and long-term follow-up is needed to assess for potential efficacy in this rare disease.

Study Overview

• Status: Active, not recruiting
• Conditions: Spinocerebellar Ataxias
• Intervention / Treatment: Drug: BHV-4157

Detailed Description

This study comprises multiple sources of RWD including: 1) the Clinical Research Consortium for the Study of Cerebellar Ataxia (CRC-SCA/US SCA Natural History cohort; 2) the European Integrated Project on Spinocerebellar Ataxias (EUROSCA/European SCA Natural History Cohort); and 3) the 3 year OLE data from troriluzole treated subjects in Study BHV4157-206 (NCT03701399). Each participant of the study will have their efficacy and/or safety data collected as pre-specified in the original protocols from the RWD sources.

The effectiveness of troriluzole in SCA after 3 years of treatment from the long-term, open-label extension from Study BHV4157-206 will be compared to external control subjects collected from CRC-SCA (US SCA Natural History cohort) and EUROSCA (European SCA Natural History Cohort). A propensity score matching (PSM) analysis will be utilized to create equipoise across groups being examined in the analysis.

The primary outcome will be change from baseline in the modified functional Scale for the Assessment and Rating of Ataxia (f-SARA). Another endpoint examined will be a newly developed and validated composite endpoint for SCA, the Spinocerebellar Ataxia Composite Score (SCACOMS).

• Study Type: Observational
• Enrollment (Actual): 909

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Biohaven

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study involves the analysis of data collected among three research settings: 1) European registry of SCA patients (2005-2008) (NCT02440763 ); 2) US registry of SCA patients (2010-present) (NCT01060371); 3) Subjects originally randomized to troriluzole in BHV4157-206 with 3-years of treatment data (NCT03701399).

Description

Key Inclusion Criteria for troriluzole-treated participants (BHV4157-206):

• Between the ages of 18-75
• Genetic confirmation of the following specific hereditary ataxias: SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, and SCA10
• Screening f-SARA total score of ≥3 and score of ≥1 on gait item of the f-SARA.
• Ability to ambulate 8 meters without human assistance (canes and other devices were allowed)
• Subjects initially randomized to troriluzole

Key Inclusion Criteria for participants selected from the natural history studies:

• Between ages of 18-75
• CRC-SCA: either a genetic confirmation or a diagnosis of SCA 1, 2, 3, 6, 7, 8, and 10 in themselves or a family member; EUROSCA: genetic confirmation of SCA genotypes 1, 2, 3 and 6.

Key Exclusion Criteria for troriluzole-treated participants (BHV4157-206 study):

• Screening f-SARA score of 4 on any item of the f-SARA
• Any other medical condition that could predominantly explain or contribute significantly to the subjects' symptoms of ataxia or that could confound assessment of ataxia symptoms

Key Exclusion Criteria for participants selected from the natural history studies:

• Treatment with troriluzole

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Troriluzole-treated SCA subjects; The BHV4157-206 study is a Phase III, multicenter, randomized, double-blind, 2-arm, placebo-controlled parallel-group study designed to assess the safety, tolerability, and efficacy of troriluzole in a population of patients with SCA. Subjects were randomized to receive placebo (QD) or troriluzole (200 mg QD). BHV4157-206 consisted of a randomization phase and an OLE phase. Subjects in the trorilzuole-treated cohort are from study BHV4157-206, were originally randomized to troriluzole, and extended an opportunity to continue treatment in an open-label extenstion (OLE) phase. All subjects had the opportunity to complete 3-years of treatment.	Drug: BHV-4157; BHV-4157 (troriluzole) 200 mg QD
SCA Natural History Comparator; The natural history comparison group includes SCA subjects from the CRC-SCA and EUROSCA natural history studies. The CRC-SCA study includes individuals with SCA 1, 2, 3, 6, 7, 8, and 10, with the time period of data collection spanning 2010 to present. Patients taking riluzole or troriluzole in the CRC-SCA study were not included in this analysis. The EUROSCA study included individuals with SCA genotypes 1, 2, 3, and 6, with the time period of data collection spanning 2005-2009. The natural history protocols were finalized prior to our conduct of the present analysis, as each was designed for independent research purposes.

What is the study measuring?

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) at Year 3 in troriluzole-treated subjects is compared to natural history subjects from CRC-SCA	To compare the effectiveness of troriluzole in treating SCA, as measure by the modified functional Scale for the Assessment and Rating of Ataxia (f-SARA), in subjects randomized to treatment with troriluzole relative to natural history controls from the natural history dataset after 3 years of treatment. The f-SARA is a scale with a range of 0 to 16, where an increase in the total score indicates a worsening of symptoms.	Up to 3 years of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in the f-SARA at Year 2 in troriluzole-treated subjects is compared to the change from baseline in the mapped f-SARA at Year 2 in natural history subjects from CRC-SCA	The f-SARA is a scale with a range of 0 to 16, where an increase in the total score indicates a worsening of symptoms.	Up to 2 years of treatment
Change from baseline in the f-SARA at Year 1 in troriluzole-treated subjects is compared to the change from baseline in the mapped f-SARA at Year 1 in natural history subjects from CRC-SCA	The f-SARA is a scale with a range of 0 to 16, where an increase in the total score indicates a worsening of symptoms.	Up to 1 year of treatment
Change from baseline in the f-SARA at Year 3 in troriluzole-treated subjects is compared to the change from baseline in the mapped f-SARA at Year 3 in natural history subjects from EUROSCA	The f-SARA is a scale with a range of 0 to 16, where an increase in the total score indicates a worsening of symptoms.	Up to 3 years of treatment
Change from baseline in the f-SARA at Year 2 in troriluzole-treated subjects is compared to the change from baseline in the mapped f-SARA at Year 2 in natural history subjects from EUROSCA	The f-SARA is a scale with a range of 0 to 16, where an increase in the total score indicates a worsening of symptoms.	Up to 2 years of treatment
Change from baseline in the f-SARA at Year 1 in troriluzole-treated subjects is compared to the change from baseline in the mapped f-SARA at Year 1 in natural history subjects from EUROSCA	The f-SARA is a scale with a range of 0 to 16, where an increase in the total score indicates a worsening of symptoms.	Up to 1 year of treatment
Change from baseline in the f-SARA at Year 3 in troriluzole-treated subjects is compared to the change from baseline in the mapped f-SARA at Year 3 in pooled (CRC-SCA and EUROSCA) natural history subjects	The f-SARA is a scale with a range of 0 to 16, where an increase in the total score indicates a worsening of symptoms.	Up to 3 years of treatment
Change from baseline in the f-SARA at Year 2 in troriluzole-treated subjects is compared to the change from baseline in the mapped f-SARA at Year 2 in in pooled (CRC-SCA and EUROSCA) natural history subjects	The f-SARA is a scale with a range of 0 to 16, where an increase in the total score indicates a worsening of symptoms.	Up to 2 years of treatment
Change from baseline in the f-SARA at Year 1 in troriluzole-treated subjects is compared to the change from baseline in the mapped f-SARA at Year 1 in pooled (CRC-SCA and EUROSCA) natural history subjects	The f-SARA is a scale with a range of 0 to 16, where an increase in the total score indicates a worsening of symptoms.	Up to 1 year of treatment
Change from baseline in Spinocerebellar Ataxia Composite Score (SCACOMS) at Year 3 in troriluzole-treated subjects is compared to that of in CRC-SCA natural history subjects	The SCACOMS (SCA Composite Scale) is a newly developed and validated endpoint for SCA, derived from an analysis of two SCA natural history studies (CRC-SCA and EUROSCA). The score range of SCACOMS is 0-50, where an increase in the total score indicates a worsening of symptoms.	Up to 3 years of treatment
Change from baseline in SCACOMS at Year 2 in troriluzole-treated subjects is compared to that of in CRC-SCA natural history subjects	The SCACOMS (SCA Composite Scale) is a newly developed and validated endpoint for SCA, derived from an analysis of two SCA natural history studies (CRC-SCA and EUROSCA). The score range of SCACOMS is 0-50, where an increase in the total score indicates a worsening of symptoms.	Up to 2 years of treatment
Change from baseline in SCACOMS at Year 1 in troriluzole-treated subjects is compared to that of in CRC-SCA natural history subjects	The SCACOMS (SCA Composite Scale) is a newly developed and validated endpoint for SCA, derived from an analysis of two SCA natural history studies (CRC-SCA and EUROSCA). The score range of SCACOMS is 0-50, where an increase in the total score indicates a worsening of symptoms.	Up to 1 year of treatment

Collaborators and Investigators

• Sponsor: Biohaven Therapeutics Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2019
• Primary Completion (Actual): September 6, 2024
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: July 26, 2024
• First Submitted That Met QC Criteria: July 30, 2024
• First Posted (Actual): July 31, 2024

Study Record Updates

• Last Update Posted (Actual): January 9, 2026
• Last Update Submitted That Met QC Criteria: January 8, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: disease registry; SCA; natural history; propensity score match; f-SARA
• 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: BHV4157-206-RWE

Drug and device information, study documents

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