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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
| |
| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BHV-4157 | Drug | BHV-4157 (troriluzole) 200 mg QD |
|
| 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 |
| 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 |
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Key Inclusion Criteria for troriluzole-treated participants (BHV4157-206):
Key Inclusion Criteria for participants selected from the natural history studies:
Key Exclusion Criteria for troriluzole-treated participants (BHV4157-206 study):
Key Exclusion Criteria for participants selected from the natural history studies:
• Treatment with troriluzole
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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).
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Biohaven | New Haven | Connecticut | 06510 | United States |
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| ID | Term |
|---|---|
| D020754 | Spinocerebellar Ataxias |
| ID | Term |
|---|---|
| D002524 | Cerebellar Ataxia |
| D002526 | Cerebellar Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| 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 |
| D009422 |
| Nervous System Diseases |
| D013132 | Spinocerebellar Degenerations |
| D013118 | Spinal Cord Diseases |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D001259 | Ataxia |
| D020820 | Dyskinesias |
| D009461 | Neurologic Manifestations |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |