Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy (ATTRibute-CM)
Amyloidosis, Amyloid Cardiomyopathy, Transthyretin Amyloidosis
About this trial
This is an interventional treatment trial for Amyloidosis focused on measuring Amyloidosis, ATTR-CM, Transthyretin, Amyloid, TTR
Eligibility Criteria
Inclusion Criteria:
- Have an established diagnosis of ATTR-CM with either wild-type TTR or variant TTR genotype
- Have a history of heart failure evidenced by at least one prior hospitalization for heart failure or clinical evidence of heart failure without prior heart failure hospitalization manifested by signs or symptoms of volume overload or elevated intracardiac pressures or heart failure symptoms that required or require ongoing treatment with a diuretic.
- New York Heart Association (NYHA) Class I-III symptoms due to ATTR cardiomyopathy.
- On stable doses of cardiovascular medical therapy
- Completed ≥150 m on the 6MWT on 2 tests that are within 15% of total distance walked prior to randomization
- Biomarkers of myocardial wall stress, NT-proBNP level ≥300 pg/mL at screening
- Have left ventricular wall (interventricular septum or left ventricular posterior wall) thickness ≥12 mm
Exclusion Criteria:
- Had acute myocardial infarction, acute coronary syndrome or coronary revascularization, or experienced stroke or transient ischemic attack within 90 days prior to screening
- Has hemodynamic instability
- Likely to undergo heart transplantation within a year of screening
- Confirmed diagnosis of primary (light chain) amyloidosis
- Biomarkers of myocardial wall stress, NT-proBNP level ≥8500 pg/mL at screening
- Measure of kidney function, eGFR by MDRD formula <15 mL/min/1.73 m2
- Current treatment with marketed drug products and other investigational agents for the treatment of ATTR-CM
- Current treatment with calcium channel blockers with conduction system effects (e.g. verapamil, diltiazem). The use of dihydropyridine calcium channel blockers is allowed. The use of digitalis will only be allowed if required for management of atrial fibrillation with rapid ventricular response
Sites / Locations
- Cedars-Sinai Medical Center
- Pacific Heart Institute
- University of Colorado Hospital - Anschutz Medical Campus
- Yale School of Medicine
- MedStar Washington Hospital Center
- University of Miami - Sylvester Comprehensive Cancer Center
- Piedmont Heart Institute Athens
- Emory Heart and Vascular Center
- Northwestern University
- The University of Chicago Medical Center
- NorthShore University Health System
- Indiana University
- MedStar Medical Group Cardiology at Franklin Square Medical Center
- Boston University School of Medicine
- Saint Elizabeth's Medical Center
- Mayo Clinic
- Saint Luke's Hospital - Kansas City
- Washington University School of Medicine
- Newark Beth Israel Medical Center
- Montefiore Medical Center
- North Shore University Hospital
- New York University Langone Health
- Mount Sinai Hospital
- Columbia University Medical Center
- Laurelton Heart Specialist
- University of North Carolina - Chapel Hill
- Duke University Health System
- Cleveland Clinic
- Oregon Health and Science University
- Penn Presbyterian Medical Center
- Allegheny General Hospital
- University of Pittsburgh
- The Medical University of South Carolina
- Prisma Health - Greenville Memorial Hospital
- University of Texas Southwestern Medical Center
- University of Utah
- Virginia Commonwealth University Medical Center
- Carilion Clinic Roanoke Heart Institute
- University of Washington School of Medicine
- Providence Sacred Heart Medical Center
- Royal Adelaide Hospital
- Box Hill Hospital
- Royal Hobart Hospital
- Fiona Stanley Hospital
- Saint Vincent's Hospital Sydney
- Princess Alexandra Hospital
- Ziekenhuis Oost-Limburg - Campus Sint-Jan
- Jessa Ziekenhuis - Campus Virga Jesse
- Algemeen Ziekenhuis Sint-Jan Brugge-Oostende
- Onze-Lieve-Vrouw Ziekenhuis Aalst
- Universitair Ziekenhuis Leuven
- Hospital Cárdio Pulmonar
- Santa Casa de Misericordia - Porto Alegre
- CAPED - Centro Avançado de Pesquisa e Estudos para o Diagnóstico
- INCOR
- Instituto de Cardiologia do Rio Grande do Sul
- University of Calgary
- University of British Columbia
- CancerCare Manitoba - St. Boniface
- Halifax Infirmary
- Toronto Heart Centre
- University of Toronto
- Centre Hospitalier de L'Universite de Montreal - Hôpital Notre-Dame
- Hôpital du Sacré-Coeur de Montréal
- Institut Universitaire de Cardiologie et de Pneumologie de Québec
- Hôpital régional de Rimouski
- Montreal Heart Institute
- St. Anne´s University Hospital
- General University Hospital in Prague
- Institute for Clinical and Experimental Medicine
- Aarhus Universitetshospital
- Alexandra General Hospital of Athens
- Mater Misericordiae University Hospital
- Saint Vincents University Hospital
- Hadassah University Hospital Ein Kerem
- The Chaim Sheba Medical Center
- Ospedale San Donato
- Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola-Malpighi
- Azienda Ospedaliero - Universitaria Careggi
- Fondazione IRCCS Policlinico San Matteo
- Fondazione Toscana Gabriele Monasterio per la Ricerca Medica e di Sanità Pubblica
- Ospedale degli Infermi
- Universita degli Studi di Roma La Sapienza - Umberto I Policlinico di Roma
- Seoul National University Bundang Hospital
- Seoul National University Hospital
- Maastricht Universitair Medisch Centrum
- Universitair Medisch Centrum Groningen
- Universitair Medisch Centrum Utrecht
- Middlemore Hospital
- Waikato Hospital
- National Institute of Cardiology
- Centro Hospitalar de Lisboa Norte EPE- Hospital Santa Maria
- Centro Hospitalar do Porto
- Clínica Universidad de Navarra
- Hospital Universitari Germans Trias i Pujol
- Hospital Juan Ramón Jiménez
- Hospital Juan Ramón Jiménez
- Clinica Universidad de Navarra Madrid
- Hospital Universitario Puerta de Hierro
- Hospital Son Llàtzer
- Hospital Clínico Universitario de Santiago de Compostela
- Hospital Clínico Universitario de Valencia
- Royal Free Hospital
- Richmond Pharmacology
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
acoramidis HCl 800 mg
Placebo
Subjects will receive acoramidis HCl 800 mg twice daily. 6MWT primary outcome will be assessed at the end of 12 months. The hierarchical combination of All-Cause mortality, cumulative frequency of cardiovascular-related hospitalizations, change from baseline in NT-proBNP levels, and change from baseline in distance walked on the 6MWT will be assessed after 30 months of treatment.
Subjects will receive placebo to match twice daily. 6MWT primary outcome will be assessed at the end of 12 months. The hierarchical combination of All-Cause mortality, cumulative frequency of cardiovascular-related hospitalizations, change from baseline in NT-proBNP levels, and change from baseline in distance walked on the 6MWT will be assessed after 30 months of treatment.