real-world data study of troriluzole-treated patients with spinocerebellar ataxia (sca) compared to a matched natural history control

Conditions: Spinocerebellar Ataxias

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.

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

Keywords: propensity score match natural history disease registry sca f-sara