Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy

NCT03860935 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: AG10-3012018-004280-32
• Study Type: interventional
• Target: 632
• Locations: 18 countries
• Sites: 104

Brief Summary

Phase 3 efficacy and safety study to evaluate acoramidis (AG10) HCl 800 mg administered orally twice a day compared to placebo in subjects with symptomatic Transthyretin Amyloid Cardiomyopathy (ATTR-CM).

Conditions

Amyloidosis; Amyloid Cardiomyopathy; Transthyretin Amyloidosis; Cardiomyopathies; Heart Diseases

Keywords

Amyloidosis; ATTR-CM; Transthyretin; Amyloid; TTR

Outcome Measures

Primary Outcomes (1)

• A Hierarchical Combination of All-Cause Mortality, Cumulative Frequency of CV-related Hospitalization, Change From Baseline in NT-proBNP and Change From Baseline in 6MWT at the Last Available Visit Where Both Subjects Had Non-missing Assessments.

  The endpoint was analyzed using Finkelstein-Schoenfeld method. The method combines all-cause mortality, cumulative frequency of CV-related hospitalizations, change from baseline in NT-proBNP and change from baseline in 6MWT in a hierarchical fashion. The method compares every participant with every other participant within strata, assigning a +1 to the "better" participant and a -1 to the "worse" participant and 0 if they are "tied". Participants who had heart transplantation or implantation of a cardiac mechanical assist device were handled in the same manner as death. 'Win' represents a participant doing better based on hierarchical comparison. The reported unit is the total percent of "wins" for each treatment group from performing such a hierarchical comparison across stratification factors in the study.

  Baseline up to Month 30

Secondary Outcomes (4)

• Change From Baseline to Month 30 in the Distance Walked During the 6 Minute Walk Test (6MWT)

  Month 30

• Change From Baseline to Month 30 of the Kansas City Cardiomyopathy Questionnaire Overall Score (KCCQ-OS)

  Month 30

• Change From Baseline to Month 30 in Serum TTR (Prealbumin) Level

  Month 30

• All-cause Mortality by Month 30, Including Death Due to Any Cause, Heart Transplant or Cardiac Mechanical Assist Device (CMAD)

  Baseline up to Month 30

Study Arms (2)

acoramidis HCl 800 mg

EXPERIMENTAL

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.

Drug: acoramidis

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo Oral Tablet

Interventions

acoramidis DRUG

TTR stabilizer administered orally twice daily (BID)

Also known as: AG10, ALXN2060

acoramidis HCl 800 mg

Placebo Oral Tablet DRUG

Non-active control administered orally twice daily (BID)

Placebo

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eidos Therapeutics, a BridgeBio company: lead

Study Sites (104)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Pacific Heart Institute

Santa Monica, California, 90404, United States

Location

University of Colorado Hospital - Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Yale School of Medicine

New Haven, Connecticut, 06473, United States

Location

MedStar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

University of Miami - Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Piedmont Heart Institute Athens

Athens, Georgia, 30606, United States

Location

Emory Heart and Vascular Center

Atlanta, Georgia, 30322, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

The University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

NorthShore University Health System

Evanston, Illinois, 60201, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

MedStar Medical Group Cardiology at Franklin Square Medical Center

Baltimore, Maryland, 21218, United States

Location

Boston University School of Medicine

Boston, Massachusetts, 02118, United States

Location

Saint Elizabeth's Medical Center

Boston, Massachusetts, 02135, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Saint Luke's Hospital - Kansas City

Kansas City, Missouri, 64111, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Newark Beth Israel Medical Center

Newark, New Jersey, 07112, United States

Location

North Shore University Hospital

Manhasset, New York, 11030, United States

Location

New York University Langone Health

New York, New York, 10010, United States

Location

Mount Sinai Hospital

New York, New York, 10029, United States

Location

Columbia University Medical Center

New York, New York, 10034, United States

Location

Laurelton Heart Specialist

Rosedale, New York, 11422, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

Duke University Health System

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, 19104, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

The Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Prisma Health - Greenville Memorial Hospital

Greenville, South Carolina, 29605, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Virginia Commonwealth University Medical Center

Richmond, Virginia, 23298, United States

Location

Carilion Clinic Roanoke Heart Institute

Roanoke, Virginia, 24014, United States

Location

University of Washington School of Medicine

Seattle, Washington, 98195, United States

Location

Providence Sacred Heart Medical Center

Spokane, Washington, 99204, United States

Location

Royal Adelaide Hospital

Adelaide, Australia

Location

Box Hill Hospital

Box Hill, Australia

Location

Royal Hobart Hospital

Hobart, Australia

Location

Fiona Stanley Hospital

Murdoch, Australia

Location

Saint Vincent's Hospital Sydney

Sydney, 2010, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Australia

Location

Ziekenhuis Oost-Limburg - Campus Sint-Jan

Genk, Limburg, Belgium

Location

Jessa Ziekenhuis - Campus Virga Jesse

Hasselt, Limburg, Belgium

Location

Algemeen Ziekenhuis Sint-Jan Brugge-Oostende

Bruges, West Vlaanderen, Belgium

Location

Onze-Lieve-Vrouw Ziekenhuis Aalst

Aalst, Belgium

Location

Universitair Ziekenhuis Leuven

Leuven, Belgium

Location

Hospital Cárdio Pulmonar

Salvador, Estado de Bahia, Brazil

Location

Santa Casa de Misericordia - Porto Alegre

Porto Alegre, Rio Grande do Sul, 90020-090, Brazil

Location

CAPED - Centro Avançado de Pesquisa e Estudos para o Diagnóstico

Ribeirão Preto, São Paulo, 14026-900, Brazil

Location

INCOR

São Paulo, São Paulo, Brazil

Location

Instituto de Cardiologia do Rio Grande do Sul

Porto Alegre, Brazil

Location

University of Calgary

Calgary, Alberta, T2N 4Z6, Canada

Location

University of British Columbia

Vancouver, British Columbia, V5Z 1M9, Canada

Location

CancerCare Manitoba - St. Boniface

Winnipeg, Manitoba, Canada

Location

Halifax Infirmary

Halifax, Nova Scotia, B3H 3A7, Canada

Location

Toronto Heart Centre

Toronto, Ontario, M4P 1E4, Canada

Location

University of Toronto

Toronto, Ontario, M5G 2N2, Canada

Location

Centre Hospitalier de L'Universite de Montreal - Hôpital Notre-Dame

Montreal, Quebec, H2X 3H8, Canada

Location

Hôpital du Sacré-Coeur de Montréal

Montreal, Quebec, H4J 1C5, Canada

Location

Institut Universitaire de Cardiologie et de Pneumologie de Québec

Québec, Quebec, G1V 4G5, Canada

Location

Hôpital régional de Rimouski

Rimouski, Quebec, G5L 5T1, Canada

Location

Montreal Heart Institute

Montreal, Canada

Location

St. Anne´s University Hospital

Brno-střed, Czechia

Location

General University Hospital in Prague

New Town, Czechia

Location

Institute for Clinical and Experimental Medicine

Prague, Czechia

Location

Aarhus Universitetshospital

Aarhus, Dinamarca, 8200, Denmark

Location

Alexandra General Hospital of Athens

Athens, Attica, Greece

Location

Mater Misericordiae University Hospital

Dublin, Ireland

Location

Saint Vincents University Hospital

Dublin, Ireland

Location

Hadassah University Hospital Ein Kerem

Jerusalem, Israel

Location

The Chaim Sheba Medical Center

Tel Litwinsky, Israel

Location

Ospedale San Donato

Arezzo, Italy

Location

Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola-Malpighi

Bologna, Italy

Location

Azienda Ospedaliero - Universitaria Careggi

Florence, Italy

Location

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

Location

Fondazione Toscana Gabriele Monasterio per la Ricerca Medica e di Sanità Pubblica

Pisa, Italy

Location

Ospedale degli Infermi

Rimini, Italy

Location

Universita degli Studi di Roma La Sapienza - Umberto I Policlinico di Roma

Roma, Italy

Location

Maastricht Universitair Medisch Centrum

Maastricht, Limburg, 6229 HX, Netherlands

Location

Universitair Medisch Centrum Groningen

Groningen, Netherlands

Location

Universitair Medisch Centrum Utrecht

Utrecht, Netherlands

Location

Middlemore Hospital

Otahuhu, Auckland, 1640, New Zealand

Location

Waikato Hospital

Hamilton, Waikato Region, 3240, New Zealand

Location

National Institute of Cardiology

Warsaw, Poland

Location

Centro Hospitalar de Lisboa Norte EPE- Hospital Santa Maria

Lisbon, Portugal

Location

Centro Hospitalar do Porto

Porto, 4099-001, Portugal

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

Seoul National University Hospital

Seoul, Gyeonggi-do, 13620, South Korea

Location

Clínica Universidad de Navarra

Pamplona, Navarre, Spain

Location

Hospital Universitari Germans Trias i Pujol

Barcelona, Spain

Location

Hospital Juan Ramón Jiménez

Huelva, 21005, Spain

Location

Hospital Juan Ramón Jiménez

Huelva, Spain

Location

Clinica Universidad de Navarra Madrid

Madrid, Spain

Location

Hospital Universitario Puerta de Hierro

Madrid, Spain

Location

Hospital Son Llàtzer

Palma de Mallorca, Spain

Location

Hospital Clínico Universitario de Santiago de Compostela

Santiago de Compostela, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, Spain

Location

Royal Free Hospital

London, England, NW3 2PF, United Kingdom

Location

Richmond Pharmacology

London, SE1 1YR, United Kingdom

Location

Related Publications (8)

• 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. A plain language review of the ATTRibute-CM study: efficacy and safety of acoramidis in transthyretin amyloid cardiomyopathy. Future Cardiol. 2025 Dec;21(12):1017-1025. doi: 10.1080/14796678.2025.2591426. Epub 2025 Dec 12.

  PMID: 41384357 DERIVED

• Alexander KM, Davis MK, Akinboboye O, Berk J, Bhatt K, Cappelli F, Cuddy SAM, Fontana M, Garcia-Pavia P, Gillmore JD, Griffin JM, Grodin JL, Judge DP, Khouri MG, Lam K, Masri A, Maurer MS, Obici L, Ruberg FL, Sarswat N, Shah K, Soman P, Stern L, Wright R, Xiong K, Cao X, Lystig T, Tamby JF, Castano A, Katz L, Sinha U, Fox JC, Solomon SD, Grogan M. Efficacy of Acoramidis in Wild-Type and Variant Transthyretin Amyloid Cardiomyopathy: Results From ATTRibute-CM and Its Open-Label Extension. JAMA Cardiol. 2025 Nov 8:e254477. doi: 10.1001/jamacardio.2025.4477. Online ahead of print.

  PMID: 41205147 DERIVED

• 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 Nov;25(6):829-839. doi: 10.1007/s40256-025-00752-x. Epub 2025 Aug 1.

  PMID: 40750720 DERIVED

• 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.

  PMID: 40398971 DERIVED

• 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.

  PMID: 40074465 DERIVED

• 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.

  PMID: 39878480 DERIVED

• 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.

  PMID: 38197816 DERIVED

• 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.

  PMID: 33725199 DERIVED

MeSH Terms

Conditions

Amyloidosis; Amyloid Neuropathies, Familial; Amyloidosis, Hereditary, Transthyretin-Related; Cardiomyopathies; Heart Diseases; Alzheimer Disease

Interventions

attruby

Condition Hierarchy (Ancestors)

Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Amyloid Neuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Amyloidosis, Familial; Metabolism, Inborn Errors; Cardiovascular Diseases; Dementia; Brain Diseases; Central Nervous System Diseases; Tauopathies; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: VP, Clinical Operations
• Organization: Eidos Therapeutics, Inc., a BridgeBio Company

info@bridgebio.com

415-887-1471

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2019
• First Posted: March 4, 2019
• Study Start: March 19, 2019
• Primary Completion: May 11, 2023
• Study Completion: May 11, 2023
• Last Updated: June 27, 2024
• Results First Posted: June 27, 2024

Record last verified: 2024-06

Locations

US (40); CA (11); IT (7); NL (3); PT (2); IL (2); GR (1); CZ (3); NZ (2); PL (1); DK (1); AU (6); BR (5); ES (9); IE (2); BE (5); KR (2); GB (2)