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.
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
909
BHV-4157 (troriluzole) 200 mg QD
Biohaven
New Haven, Connecticut, United States
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.
Time frame: 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 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Up to 1 year of treatment
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