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

Active, not recruiting
Conditions
Spinocerebellar Ataxias
Interventions
Registration Number
NCT06529146
Lead Sponsor
Biohaven Therapeutics Ltd.
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).

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
909
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Troriluzole-treated SCA subjectsBHV-4157The 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.
Primary Outcome Measures
NameTimeMethod
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-SCAUp 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 Outcome Measures
NameTimeMethod
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 EUROSCAUp 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 Spinocerebellar Ataxia Composite Score (SCACOMS) at Year 3 in troriluzole-treated subjects is compared to that of in CRC-SCA natural history subjectsUp 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 1 in troriluzole-treated subjects is compared to that of in CRC-SCA natural history subjectsUp 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.

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-SCAUp 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 EUROSCAUp 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 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 subjectsUp 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 CRC-SCAUp 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 EUROSCAUp 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 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 subjectsUp 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 subjectsUp 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 SCACOMS at Year 2 in troriluzole-treated subjects is compared to that of in CRC-SCA natural history subjectsUp 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.

Trial Locations

Locations (1)

Biohaven

🇺🇸

New Haven, Connecticut, United States

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