Clinical trial NCT06529146: Real-World Data Study of Troriluzole-Treated Patients With Spinocerebellar Ataxia (SCA) Compared to a Matched Natural History Control
Official title: 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
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Spinocerebellar Ataxias
Keywords: propensity score match
natural history
disease registry
SCA
f-SARA
Lead sponsor: Biohaven Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2024-07-31
Enrollment: 909
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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).

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).

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

• Treatment with troriluzole

Primary outcomes:
measure: 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
timeFrame: Up to 3 years of treatment
Secondary outcomes:
measure: 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
timeFrame: Up to 2 years of treatment
measure: 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
timeFrame: Up to 1 year of treatment
measure: 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
timeFrame: Up to 3 years of treatment
measure: 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
timeFrame: Up to 2 years of treatment
measure: 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
timeFrame: Up to 1 year of treatment
measure: 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
timeFrame: Up to 3 years of treatment
measure: 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
timeFrame: Up to 2 years of treatment
measure: 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
timeFrame: Up to 1 year of treatment
measure: 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
timeFrame: Up to 3 years of treatment
measure: Change from baseline in SCACOMS at Year 2 in troriluzole-treated subjects is compared to that of in CRC-SCA natural history subjects
timeFrame: Up to 2 years of treatment
measure: Change from baseline in SCACOMS at Year 1 in troriluzole-treated subjects is compared to that of in CRC-SCA natural history subjects
timeFrame: Up to 1 year of treatment
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Biohaven
state: Connecticut
Study officials:
References: