Spinocerebellar Ataxias
Conditions
Keywords
propensity score match, natural history, disease registry, SCA, f-SARA
Brief summary
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.
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).
Interventions
DRUGBHV-4157
BHV-4157 (troriluzole) 200 mg QD
Sponsors
Biohaven Therapeutics Ltd.
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Up to 3 years of treatment | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Up to 2 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. |
| 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 | Up to 1 year 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. |
| 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 | Up to 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. |
| 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 | Up to 2 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. |
| 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 | Up to 1 year 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. |
| 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 | Up to 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. |
| 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 | Up to 2 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. |
| 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 | Up to 1 year 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. |
| 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 | Up to 3 years of treatment | 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. |
| Change from baseline in SCACOMS at Year 2 in troriluzole-treated subjects is compared to that of in CRC-SCA natural history subjects | Up to 2 years of treatment | 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. |
| Change from baseline in SCACOMS at Year 1 in troriluzole-treated subjects is compared to that of in CRC-SCA natural history subjects | Up to 1 year of treatment | 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. |
Countries
United States
Outcome results
None listed