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ACO-SWITCH: Rationale and Design of a Phase 4 Study Evaluating Serum Transthyretin in ATTR-CM After Switching from
Roman Pfister1, Lars Michel2, Marcel Schulze3
1Department III of Internal Medicine, Heart Center, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany. roman.pfister@uk-koeln.de.
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.
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