Transthyretin Amyloid Cardiomyopathy (ATTR-CM)
Conditions
Interventions
Test Product, Dosage, and Mode of Administration:
Day 1 through end of Double-blind Treatment: 800 mg acoramidis hydrochloride
(HCl) or matching placebo, BID, by mouth
Sponsors
Eidos Therapeutics, Inc.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: To be eligible to participate in the study, subjects must meet all the following criteria: 1. Have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures. 2. Male or female >= 18 to = 150 m on the 6MWT on at least 2 tests > 24 hours to = 150 m or the first two tests are not within 15% of distance walked, a third test must be conducted = 150 m or within 15% of one of the first two tests, the subject will not be eligible for participation. 9. Must have NT-proBNP levels >= 300 pg/mL at Screening. 10. Must have LV wall (interventricular septum or LV posterior wall) thickness >= 12 mm as measured by transthoracic echocardiogram (ECHO) or cardiac magnetic resonance (CMR) documented in medical history within 10 years of Screening or at Screening ECHO or CMR.
Exclusion criteria
Exclusion criteria: Subjects who meet any of the following criteria at the Screening visit will not be eligible to participate in the study: 1. Acute myocardial infarction, acute coronary syndrome or coronary revascularization within 90 days prior to Screening. 2. Stroke or transient ischemic attack (TIA) within 90 days prior to Screening. 3. Has hemodynamic instability at Screening or Randomization that, in the judgment of the Investigator, would pose too great a risk for participation in the study. 4. Is likely to undergo heart transplantation within a year of Screening. 5. Has confirmed diagnosis of light-chain (AL) amyloidosis. 6. Has abnormal liver function tests at Screening, defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 × upper limit of normal (ULN) or total bilirubin > 3 × ULN. 7. Has NT-proBNP levels >= 8500 pg/mL at Screening. 8. Has estimated glomerular filtration rate (eGFR) by modification of diet for renal disease (MDRD) formula
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Key Primary Part A • Change from baseline to Month 12 of treatment in distance walked during the 6MWT Part B • A hierarchical combination of All-Cause mortality, CV-related hospitalization, and change from baseline in 6MWT over a 30-month period | — |
Secondary
| Measure | Time frame |
|---|---|
| Key Secondary Part A • Change from baseline to Month 12 of treatment in Kansas City Cardiomyopathy Questionnaire Overall Score (KCCQ-OS) Part B • Change from baseline to Month 30 of treatment in distance walked during the 6MWT • Change from baseline to Month 30 of treatment in KCCQ-OS Secondary Part A • Safety parameters to be assessed: treatment- emergent serious adverse events (SAEs) and adverse events (AEs), AEs leading to treatment discontinuation, abnormal physical exam findings of clinical relevance, abnormal vital signs of clinical relevance, abnormal ECG parameters of clinical relevance, and changes in clinical safety laboratory parameters of potential clinical concern • Change from baseline in TTR (prealbumin) level (an in vivo measure of TTR stabilization) at Month 12 • TTR stabilization as measured in established ex-vivo assays (fluorescent probe exclusion [FPE] and Western blot) at Month 12 in the PK-PD substudy Part B: • A hierarchical combination of All-Cause mortality and CV-related hospitalization over a 30-month period • All-Cause Mortality by Month 30 • Cumulative frequency of CV-related hospitalization by Month 30 • CV mortality by Month 30 • Safety parameters: treatment-emergent SAEs and AEs, AEs leading to treatment discontinuation, abnormal physical exam findings of clinical relevance, abnormal vital signs of clinical relevance, abnormal ECG parameters of clinical relevance, and changes in clinical safety laboratory parameters of potential clinical concern • Change from baseline in TTR (prealbumin) level (an in vivo measure of TTR stabilization) at Month 30 • TTR stabilization measured in established ex-vivo assays (FPE and Western blot) in the PK-PD substudy | — |
Countries
Netherlands
Outcome results
None listed