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

Biohaven

Status: Active, not recruiting

Conditions: Spinocerebellar Ataxias

Treatments: Drug: BHV-4157

Study type: Observational

Funder types: Industry

Identifiers

NCT06529146

BHV4157-206-RWE

Details and patient eligibility

About

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.

Full 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).

Enrollment: 909 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

909 participants in 2 patient groups

Troriluzole-treated SCA subjects

Description:

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.

Treatment:

Drug: BHV-4157

SCA Natural History Comparator

Description:

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.