ACO-SWITCH: Rationale and Design of a Phase 4 Study Evaluating Serum Transthyretin in ATTR-CM After Switching from Tafamidis to Acoramidis.

INTRODUCTION: Acoramidis is a novel oral transthyretin (TTR) stabilizer approved for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM) based on the phase 3 ATTRibute-CM study (ClinicalTrials.gov identifier, NCT03860935). As the ATTR-CM therapy landscape evolves, there is a growing need to evaluate changes in disease markers and treatment response in patients who switch therapies. METHODS: ACO-SWITCH (NCT07298044) is an ongoing, prospective, open-label, multicenter, single-arm, interventional phase 4 study designed to evaluate the effects of switching from tafamidis to acoramidis in 50 adults with variant or wild-type ATTR-CM diagnosis within the past 24 months. Participants will have used tafamidis for ≥ 3 months prior to study start and after a 21-day screening period, will switch to a 6-month acoramidis treatment period. Data will be collected at weekly visits during the first month of acoramidis treatment, after 3 months, at the end of treatment, and 30 days after the end of treatment. PLANNED OUTCOMES: The primary endpoint is the change in serum TTR (sTTR) level from baseline to month 6 or time of premature treatment discontinuation, measured using immunoturbidimetry and analyzed using the one-sided paired Wilcoxon signed-rank test. Secondary endpoints include sTTR levels at different time points; changes from baseline to month 6 in cardiovascular (N-terminal pro-B-type natriuretic peptide, high-sensitivity troponin T, and retinol-binding protein 4), kidney (estimated glomerular filtration rate, creatinine, cystatin C, urinary albumin-to-creatinine ratio), and thyroid (thyroid-stimulating hormone) biomarkers; echocardiographic results; 6-minute walking distance; the Kansas City Cardiomyopathy Questionnaire overall summary score; the EuroQol 5-dimension 5-level index score; and adverse events. Statistical analyses for secondary endpoints will be explorative and descriptive. Descriptive analysis will be carried out using summary statistics for categorical and continuous data. CONCLUSIONS: ACO-SWITCH is a prospective study in adults with ATTR-CM. The study will determine the effects of switching treatment from tafamidis to acoramidis, with a particular focus on sTTR levels. ACO-SWITCH aims to provide evidence to support clinical decision-making and guide optimal management in patients with ATTR-CM. Graphical Abstract available for this article. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier, NCT07298044.