Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy
NCT ID: NCT03860935
Last Updated: 2024-06-27
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
632 participants
INTERVENTIONAL
2019-03-19
2023-05-11
Brief Summary
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Detailed Description
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There are two forms of ATTR-CM:
* Wild Type\* This form of the condition primarily develops in older individuals who do not carry gene mutations.
* Hereditary\* This form of the condition comes from gene mutations passed down in families.
In this study we are researching the investigational drug acoramidis HCl 800 mg administered orally twice a day. Through the study, we want to evaluate the efficacy and safety of acoramidis in patients with ATTR-CM versus placebo.
This is a 30 month, randomized, double-blind, placebo-controlled study. This means that, during the 30 month study, investigators conducting the research and study participants will not know whether the study participant is receiving acoramidis or placebo.
The primary outcomes of the study are:
1. The impact of acoramidis versus placebo on the change in distance walked on the 6 minute walk test (6MWT) after 12 months of treatment compared to baseline.
2. The impact of acoramidis versus placebo on the hierarchical combination of All-Cause mortality, cumulative frequency of cardiovascular-related hospitalizations, change from baseline in NT-proBNP, and change in from baseline in 6MWT over a 30-month fixed treatment duration.
At the end of 30 months, participants may be eligible to receive investigational acoramidis, and there is no placebo. This is called an "open label extension." This separate study may help us better understand the safety related to taking acoramidis over a longer period of time.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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acoramidis HCl 800 mg
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.
acoramidis
TTR stabilizer administered orally twice daily (BID)
Placebo
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.
Placebo Oral Tablet
Non-active control administered orally twice daily (BID)
Interventions
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acoramidis
TTR stabilizer administered orally twice daily (BID)
Placebo Oral Tablet
Non-active control administered orally twice daily (BID)
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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
18 Years
90 Years
ALL
No
Sponsors
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Eidos Therapeutics, a BridgeBio company
INDUSTRY
Responsible Party
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Locations
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Cedars-Sinai Medical Center
Los Angeles, California, United States
Pacific Heart Institute
Santa Monica, California, United States
University of Colorado Hospital - Anschutz Medical Campus
Aurora, Colorado, United States
Yale School of Medicine
New Haven, Connecticut, United States
MedStar Washington Hospital Center
Washington D.C., District of Columbia, United States
University of Miami - Sylvester Comprehensive Cancer Center
Miami, Florida, United States
Piedmont Heart Institute Athens
Athens, Georgia, United States
Emory Heart and Vascular Center
Atlanta, Georgia, United States
Northwestern University
Chicago, Illinois, United States
The University of Chicago Medical Center
Chicago, Illinois, United States
NorthShore University Health System
Evanston, Illinois, United States
Indiana University
Indianapolis, Indiana, United States
MedStar Medical Group Cardiology at Franklin Square Medical Center
Baltimore, Maryland, United States
Boston University School of Medicine
Boston, Massachusetts, United States
Saint Elizabeth's Medical Center
Boston, Massachusetts, United States
Mayo Clinic
Rochester, Minnesota, United States
Saint Luke's Hospital - Kansas City
Kansas City, Missouri, United States
Washington University School of Medicine
St Louis, Missouri, United States
Newark Beth Israel Medical Center
Newark, New Jersey, United States
North Shore University Hospital
Manhasset, New York, United States
New York University Langone Health
New York, New York, United States
Mount Sinai Hospital
New York, New York, United States
Columbia University Medical Center
New York, New York, United States
Laurelton Heart Specialist
Rosedale, New York, United States
Montefiore Medical Center
The Bronx, New York, United States
University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States
Duke University Health System
Durham, North Carolina, United States
Cleveland Clinic
Cleveland, Ohio, United States
Oregon Health and Science University
Portland, Oregon, United States
Penn Presbyterian Medical Center
Philadelphia, Pennsylvania, United States
Allegheny General Hospital
Pittsburgh, Pennsylvania, United States
University of Pittsburgh
Pittsburgh, Pennsylvania, United States
The Medical University of South Carolina
Charleston, South Carolina, United States
Prisma Health - Greenville Memorial Hospital
Greenville, South Carolina, United States
University of Texas Southwestern Medical Center
Dallas, Texas, United States
University of Utah
Salt Lake City, Utah, United States
Virginia Commonwealth University Medical Center
Richmond, Virginia, United States
Carilion Clinic Roanoke Heart Institute
Roanoke, Virginia, United States
University of Washington School of Medicine
Seattle, Washington, United States
Providence Sacred Heart Medical Center
Spokane, Washington, United States
Royal Adelaide Hospital
Adelaide, , Australia
Box Hill Hospital
Box Hill, , Australia
Royal Hobart Hospital
Hobart, , Australia
Fiona Stanley Hospital
Murdoch, , Australia
Saint Vincent's Hospital Sydney
Sydney, , Australia
Princess Alexandra Hospital
Woolloongabba, , Australia
Ziekenhuis Oost-Limburg - Campus Sint-Jan
Genk, Limburg, Belgium
Jessa Ziekenhuis - Campus Virga Jesse
Hasselt, Limburg, Belgium
Algemeen Ziekenhuis Sint-Jan Brugge-Oostende
Bruges, West Vlaanderen, Belgium
Onze-Lieve-Vrouw Ziekenhuis Aalst
Aalst, , Belgium
Universitair Ziekenhuis Leuven
Leuven, , Belgium
Hospital Cárdio Pulmonar
Salvador, Estado de Bahia, Brazil
Santa Casa de Misericordia - Porto Alegre
Porto Alegre, Rio Grande do Sul, Brazil
CAPED - Centro Avançado de Pesquisa e Estudos para o Diagnóstico
Ribeirão Preto, São Paulo, Brazil
INCOR
São Paulo, São Paulo, Brazil
Instituto de Cardiologia do Rio Grande do Sul
Porto Alegre, , Brazil
University of Calgary
Calgary, Alberta, Canada
University of British Columbia
Vancouver, British Columbia, Canada
CancerCare Manitoba - St. Boniface
Winnipeg, Manitoba, Canada
Halifax Infirmary
Halifax, Nova Scotia, Canada
Toronto Heart Centre
Toronto, Ontario, Canada
University of Toronto
Toronto, Ontario, Canada
Centre Hospitalier de L'Universite de Montreal - Hôpital Notre-Dame
Montreal, Quebec, Canada
Hôpital du Sacré-Coeur de Montréal
Montreal, Quebec, Canada
Institut Universitaire de Cardiologie et de Pneumologie de Québec
Québec, Quebec, Canada
Hôpital régional de Rimouski
Rimouski, Quebec, Canada
Montreal Heart Institute
Montreal, , Canada
St. Anne´s University Hospital
Brno střed, , Czechia
General University Hospital in Prague
New Town, , Czechia
Institute for Clinical and Experimental Medicine
Prague, , Czechia
Aarhus Universitetshospital
Aarhus, Dinamarca, Denmark
Alexandra General Hospital of Athens
Athens, Attica, Greece
Mater Misericordiae University Hospital
Dublin, , Ireland
Saint Vincents University Hospital
Dublin, , Ireland
Hadassah University Hospital Ein Kerem
Jerusalem, , Israel
The Chaim Sheba Medical Center
Tel Litwinsky, , Israel
Ospedale San Donato
Arezzo, , Italy
Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola-Malpighi
Bologna, , Italy
Azienda Ospedaliero - Universitaria Careggi
Florence, , Italy
Fondazione IRCCS Policlinico San Matteo
Pavia, , Italy
Fondazione Toscana Gabriele Monasterio per la Ricerca Medica e di Sanità Pubblica
Pisa, , Italy
Ospedale degli Infermi
Rimini, , Italy
Universita degli Studi di Roma La Sapienza - Umberto I Policlinico di Roma
Roma, , Italy
Maastricht Universitair Medisch Centrum
Maastricht, Limburg, Netherlands
Universitair Medisch Centrum Groningen
Groningen, , Netherlands
Universitair Medisch Centrum Utrecht
Utrecht, , Netherlands
Middlemore Hospital
Otahuhu, Auckland, New Zealand
Waikato Hospital
Hamilton, Waikato Region, New Zealand
National Institute of Cardiology
Warsaw, , Poland
Centro Hospitalar de Lisboa Norte EPE- Hospital Santa Maria
Lisbon, , Portugal
Centro Hospitalar do Porto
Porto, , Portugal
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, South Korea
Seoul National University Hospital
Seoul, Gyeonggi-do, South Korea
Clínica Universidad de Navarra
Pamplona, Navarre, Spain
Hospital Universitari Germans Trias i Pujol
Barcelona, , Spain
Hospital Juan Ramón Jiménez
Huelva, , Spain
Hospital Juan Ramón Jiménez
Huelva, , Spain
Clinica Universidad de Navarra Madrid
Madrid, , Spain
Hospital Universitario Puerta de Hierro
Madrid, , Spain
Hospital Son Llàtzer
Palma de Mallorca, , Spain
Hospital Clínico Universitario de Santiago de Compostela
Santiago de Compostela, , Spain
Hospital Clínico Universitario de Valencia
Valencia, , Spain
Royal Free Hospital
London, England, United Kingdom
Richmond Pharmacology
London, , United Kingdom
Countries
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References
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Dasgupta N, Poulsen SH, Emdin M, Ambardekar AV, Shah KB, Hennum L, Marwah R, Allison M, Shivanna P, Siddhanti S, Tamby JF, Falvey H, Grodin JL. Contemporary Oral Medication Use and Frequency in Patients with Transthyretin Amyloid Cardiomyopathy. Am J Cardiovasc Drugs. 2025 Aug 1. doi: 10.1007/s40256-025-00752-x. Online ahead of print.
Maurer MS, Judge DP, Gillmore JD, Garcia-Pavia P, Masri A, Cappelli F, Alexander KM, Sarswat N, Grogan M, Ambardekar AV, Ducharme A, Poulsen SH, Lam K, Obici L, Soman P, Rao S, Tamby JF, Castano A, Fox JC, Adam B, Chepyala SR, Poland B, Sinha U, Fontana M. Early Increase in Serum Transthyretin by Acoramidis Independently Predicts Improved Survival in TTR Amyloid Cardiomyopathy. J Am Coll Cardiol. 2025 May 27;85(20):1911-1923. doi: 10.1016/j.jacc.2025.03.542.
Judge DP, Alexander KM, Cappelli F, Fontana M, Garcia-Pavia P, Gibbs SDJ, Grogan M, Hanna M, Masri A, Maurer MS, Obici L, Soman P, Cao X, Lystig T, Tamby JF, Siddhanti S, Castano A, Katz L, Fox JC, Mahaffey KW, Gillmore JD. Efficacy of Acoramidis on All-Cause Mortality and Cardiovascular Hospitalization in Transthyretin Amyloid Cardiomyopathy. J Am Coll Cardiol. 2025 Mar 18;85(10):1003-1014. doi: 10.1016/j.jacc.2024.11.042.
Soman P, Khouri MG, Lenihan D, Reyentovich A, Sperry BW, Sowalsky K, Bai Y, Du J, Katz L, Siddhanti S, Fox JC. Comparison of in-clinic assessment of 6MWT by conventional method and using wearable sensors for patients with ATTR-CM. Future Cardiol. 2025 Feb;21(2):75-81. doi: 10.1080/14796678.2025.2457881. Epub 2025 Jan 29.
Gillmore JD, Judge DP, Cappelli F, Fontana M, Garcia-Pavia P, Gibbs S, Grogan M, Hanna M, Hoffman J, Masri A, Maurer MS, Nativi-Nicolau J, Obici L, Poulsen SH, Rockhold F, Shah KB, Soman P, Garg J, Chiswell K, Xu H, Cao X, Lystig T, Sinha U, Fox JC; ATTRibute-CM Investigators. Efficacy and Safety of Acoramidis in Transthyretin Amyloid Cardiomyopathy. N Engl J Med. 2024 Jan 11;390(2):132-142. doi: 10.1056/NEJMoa2305434.
Stern LK, Kittleson MM. Updates in Cardiac Amyloidosis Diagnosis and Treatment. Curr Oncol Rep. 2021 Mar 16;23(4):47. doi: 10.1007/s11912-021-01028-8.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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2018-004280-32
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
AG10-301
Identifier Type: -
Identifier Source: org_study_id
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