Acoramidis Transthyretin Amyloidosis Prevention Trial in the Young (ACT-EARLY) Study in Asymptomatic Carriers of a Pathogenic TTR Variant

A Phase 3, Randomized, Multicenter, Double-Blind, Placebo-Controlled Study of Acoramidis for Transthyretin Amyloidosis Prevention in the Young (ACT-EARLY Trial)

Transthyretin amyloidosis (ATTR) is a disease where the normally occurring transthyretin (TTR) protein falls apart and forms amyloid, a sticky plaque-like substance that accumulates in different organs in the body and can cause damage to the organ. There are two ways that the TTR protein can fall apart. One way occurs as a person ages, where the normal TTR protein can fall apart and form amyloid that may no longer be sufficiently cleared by the body. This type of ATTR is known as wild-type ATTR (ATTRwt). The other way occurs when a person inherits a defective TTR gene that causes the TTR protein to spontaneously fall apart. This form of the disease is known as variant ATTR (ATTRv) and can be detected in adults by a genetic test of their TTR gene before they age.

Amyloid build-up in the heart causes the heart wall to become thick and stiff and can result in heart failure and even death. Accumulation of TTR amyloid in the heart is known as transthyretin amyloid cardiomyopathy or ATTR-CM. Amyloid can also deposit in the nerve tissues leading to nerve problems. Accumulation of TTR in the nerves is known as transthyretin amyloid polyneuropathy or ATTR-PN.

Acoramidis is an experimental drug designed to bind tightly to TTR in the blood and stabilize its structure, so it does not form the harmful amyloid plaques that can cause damage to organs.

This study is intended to determine if treatment with acoramidis in participants with ATTRv who have not yet developed any symptoms of disease can prevent or delay the development of ATTR-CM or ATTR-PN disease. If adults with an inherited defective TTR gene are treated early before any of the symptoms of disease have developed, it may be possible to delay the onset or prevent the disease entirely.

Study Overview

• Status: Recruiting
• Conditions: Heart Diseases; Amyloidosis; Cardiomyopathies; Polyneuropathies; Transthyretin Amyloidosis; Amyloid Cardiomyopathy
• Intervention / Treatment: Drug: Acoramidis; Drug: Placebo oral tablet

Detailed Description

The AG10-501 ACT-EARLY study is a randomized, multicenter, double-blind, placebo-controlled study of acoramidis for prevention of ATTR (with specific reference to either its cardiomyopathic or polyneuropathic manifestations). Participants will be stratified at randomization.

The study population will be asymptomatic carriers of a known pathogenic TTR gene variant. A participant must be 18 to 75 inclusive years of age, and the age of the participant must be within 10 years younger than or older than the predicted age of disease onset (PADO) based either on family history (pedigree analysis) or, if family history is insufficient, based on a TTR Variant Actuarial table from published literature. For example, if PADO for a given individual is found to be 50 years, the age of the participant must be between 40 and 75 years inclusive.

• Study Type: Interventional
• Enrollment (Estimated): 587
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Medical Information; Phone Number: 1-844-550-2246; Email: medinfo@eidostx.com

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1280AEB
    • Recruiting
    • Hospital Britanico de Buenos Aires
  • Buenos Aires, Argentina, C1199ABB
    • Recruiting
    • Hospital Italiano de Buenos Aires
• Australia
  • Darlinghurst, Australia, 2010
    • Recruiting
    • St Vincent's Hospital Sydney
  • Murdoch, Australia, 6150
    • Recruiting
    • Fiona Stanley Hospital
  • Westmead, Australia, NSW 2145
    • Recruiting
    • Westmead Hospital
  • Woolloongabba, Australia, 4102
    • Recruiting
    • Princess Alexandra Hospital
• Belgium
  • Leuven, Belgium, 3000
    • Recruiting
    • UZ Leuven
• Brazil
  • Campinas, Brazil, 13083-190
    • Recruiting
    • Fundacao Centro Medico de Campinas
  • Cerqueira César, Brazil, 05403-000
    • Recruiting
    • Instituto do Coracao (InCor) do Hospital das Clinicas da FMUSP
  • Ribeirão Preto, Brazil, 14026-900
    • Recruiting
    • CAPED - Centro Avancado de Pesquisa, Estudos e Diagnostico
  • Salvador, Brazil, 40170-130
    • Recruiting
    • Cardiopulmonar da Bahia S.A. (Hospital Cardio Pulmonar)
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • Recruiting
      • University of Calgary
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z1Y6
      • Recruiting
      • University of British Columbia
  • Ontario
    • Toronto, Ontario, Canada, M5B1W8
      • Recruiting
      • St. Michael's Hospital
• Denmark
  • Aarhus, Denmark, 8200
    • Recruiting
    • Hvitfeldt Poulsen
• France
  • Bordeaux, France, 33076
    • Recruiting
    • CHU bordeaux - Hopital Pellegrin
  • Créteil, France, 94000
    • Recruiting
    • AP-HP Hopital Henri Mondor
  • Le Kremlin-Bicêtre, France, 94270
    • Recruiting
    • AP-HP Hôpital Bicêtre
  • Rennes, France, 35000
    • Recruiting
    • CHU Rennes
  • Toulouse, France, 31400
    • Recruiting
    • CHU de Toulouse - Hôpital Rangueil
• Germany
  • Berlin, Germany, 10117
    • Recruiting
    • Charité Universitaetsmedizin Berlin
  • Heidelberg, Germany, 69120
    • Recruiting
    • Universitaetsklinikum Heidelberg
  • Mainz, Germany, 55131
    • Recruiting
    • Universitaetsmedizin der Johannes Gutenberg - Universitaet Mainz
• Greece
  • Athens, Greece, 11527
    • Recruiting
    • Hippokration General Hospital of Athens
  • Athens, Greece, 11528
    • Recruiting
    • General Hospital of Athens - Alexandra
• Ireland
  • Dublin, Ireland, D24 NR04
    • Recruiting
    • Tallaght University Hospital - The Adelaide and Meath Hospital
  • Dublin, Ireland, D07 R2WY
    • Recruiting
    • The Mater Misericordiae University Hospital
• Italy
  • Bologna, Italy, 40138
    • Recruiting
    • Azienda Ospedaliero-Universitaria di Bologna IRCCS Policlinico di S.Orsola
  • Florence, Italy
    • Recruiting
    • Azienda Ospedaliero-Universitaria Careggi
  • Pavia, Italy, 27100
    • Recruiting
    • Fondazione IRCCS Policlinico San Matteo
  • Pisa, Italy, 56124
    • Recruiting
    • Fondazione Toscana Gabriele Monasterio per la Ricerca Medica e di Sanità Pubblica - Ospedale San Cataldo
  • Roma, Italy, 00161
    • Recruiting
    • Azienda Ospedaliero Universitaria Policlinico Umberto I
  • Rome, Italy, 00189
    • Recruiting
    • Azienda Ospedaliero-Universitaria Sant'Andrea
  • Rome, Italy, 00168
    • Recruiting
    • Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore
• Japan
  • Kumamoto, Japan, 860-8556
    • Recruiting
    • Kumamoto University Hospital
  • Nagano, Japan, 390-8621
    • Recruiting
    • Shinshu University Hospital
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • Recruiting
    • University Malaya Medical Centre (UMMC)
• Martinique
  • Fort-de-France, Martinique, 97261
    • Recruiting
    • CHU de Fort de France
• Mexico
  • Tlalpan, Mexico, 14080
    • Recruiting
    • National Institute of Medical Sciences and Nutrition - Salvador Zubiran(INCMNSZ)
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Recruiting
    • University Medical Center Groningen
  • Maastricht, Netherlands, 6229 HX
    • Recruiting
    • Maastricht University Medical Center
  • Rotterdam, Netherlands, 3015 GD
    • Recruiting
    • Erasmus MC
  • Utrecht, Netherlands, 3584 CX
    • Recruiting
    • Universitair Medisch Centrum Utrecht
• Portugal
  • Lisbon, Portugal, 1649-035
    • Recruiting
    • Unidade Local de Saude de Santa Maria EPE - Hospital de Santa Maria
  • Porto, Portugal, 4099-001
    • Recruiting
    • Unidade Local de Saude de Santo Antonio EPE - Hospital de Santo Antonio
• Singapore
  • Singapore, Singapore, 169608
    • Recruiting
    • Singapore General Hospital
  • Singapore, Singapore, 119228
    • Recruiting
    • National University Hospital - National University Health System
• South Korea
  • Seoul, South Korea, 03080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, South Korea, 03722
    • Recruiting
    • Severance Hospital, Yonsei University Health System
  • Seoul, South Korea, 06351
    • Recruiting
    • Samsung Medical Center
  • Seoul, South Korea, 06591
    • Recruiting
    • Seoul St. Mary's Hospital
• Spain
  • Barcelona, Spain, 08907
    • Recruiting
    • Hospital Universitari de Bellvitge
  • Huelva, Spain
    • Recruiting
    • Hospital Universitario Juan Ramon Jimenez
  • Majadahonda, Spain
    • Recruiting
    • Hospital Universitario Puerta de Hierro
  • Palma de Mallorca, Spain, 07198
    • Recruiting
    • Hospital Universitario Son LLatzer
  • Salamanca, Spain, 37007
    • Recruiting
    • Hospital Clinico Universitario de Salamanca
• Sweden
  • Umeå, Sweden, 90185
    • Recruiting
    • Norrlands universitetssjukhus (University Hospital of Umea)
• Taiwan
  • Changhua, Taiwan, 500
    • Recruiting
    • Changhua Christian Hospital - Taiwan
  • Taipei, Taiwan, 11217
    • Recruiting
    • Taipei Veterans General Hospital
  • Taipei, Taiwan, 10016
    • Recruiting
    • National Taiwan University Hospital
• United Kingdom
  • London, United Kingdom, WC1N 3BG
    • Recruiting
    • University College London Hospitals Nhs Foundation Trust
  • London, United Kingdom, EC1A 7BE
    • Recruiting
    • St. Bartholomew's Hospital
• United States
  • California
    • La Jolla, California, United States, 92037
      • Recruiting
      • University of California, San Diego (UCSD) - Medical Center
    • Los Angeles, California, United States, 90095
      • Recruiting
      • University of California, Los Angeles (UCLA) - David Geffen School of Medicine
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California, San Francisco (UCSF)
    • Stanford, California, United States, 94305
      • Recruiting
      • Stanford University
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Anschutz
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Recruiting
      • Yale University School of Medicine - Section of Cardiology
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Recruiting
      • MedStar Washington Hospital Center - MedStar Heart and Vascular Institute
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic - Jacksonville
    • Weston, Florida, United States, 33331
      • Recruiting
      • Cleveland Clinic Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University School of Medicine
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Recruiting
      • John H. Stroger, Jr. Hospital of Cook County
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago - Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • University of Maryland Medical Center
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02118
      • Recruiting
      • Boston University (BU) School of Medicine
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Henry Ford Health System
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic - Rochester
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Recruiting
      • St. Luke's Hospital of Kansas City
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University in St. Louis
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Recruiting
      • Rutgers-Robert Wood Johnson Medical School
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Mount Sinai Hospital
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center
    • New York, New York, United States, 10016
      • Recruiting
      • New York University (NYU) School of Medicine - Langone Medical Center
    • Rosedale, New York, United States, 11422
      • Recruiting
      • Laurelton Heart Specialists
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Penn Presbyterian Medical Center
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • University of Pittsburgh Medical Center, Presbyterian Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina (MUSC)
    • Greenville, South Carolina, United States, 89605
      • Recruiting
      • Prisma Health Cancer Institute
  • Texas
    • Austin, Texas, United States, 78759
      • Recruiting
      • National Neuromuscular Research Institute
    • Dallas, Texas, United States, 75390
      • Recruiting
      • University of Texas Southwestern
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Recruiting
      • University of Utah
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Recruiting
      • Inova Fairfax Hospital
    • Richmond, Virginia, United States, 23219
      • Recruiting
      • Virginia Commonwealth University
  • Washington
    • Seattle, Washington, United States, 98195
      • Recruiting
      • University of Washington Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Male or female ≥ 18 to ≤ 75 years of age inclusive.
• Participants must have an established genotype (hetero- or homozygosity) through a medically-indicated genetic test of a TTR gene variant that is known to be pathogenic or likely pathogenic (eg, V30M/p.V50M, V122I/p.V142I, T60A/p.T80A, or all other pathogenic TTR variants).
• Participant's age is within 10 years younger than or older than PADO.

Key Exclusion Criteria:

• Evidence of ATTR-CM or ATTR-PN.
• Current or past (within last 1 to 12 months, depending on specific agent) treatment with other TTR modifying therapies.
• Contraindication to or inability to undergo cardiac magnetic resonance testing.
• Major organ dysfunction, including: kidney disease, liver disease, heart disease (including cardiomyopathy), neuropathy
• Other diseases or conditions such has cancer within 5 years, untreated hyperthyroidism or hypothyroidism, type 1 diabetes, active hepatitis B or C, HIV.
• Major surgery within the past 3 months or planned during the next 12 months.
• Known hypersensitivity to acoramidis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: acoramidis; Participants will receive acoramidis 712 mg orally BID (which is equivalent to 800 mg acoramidis HCl BID)	Drug: Acoramidis; TTR stabilizer administered orally twice daily (BID); Other Names: AG10; ALXN2060
Placebo Comparator: Placebo; Subjects will receive placebo to match twice daily	Drug: Placebo oral tablet; Non-active control administered orally twice daily (BID)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to development of ATTR (ATTR-CM or ATTR-PN, whichever occurs first; centrally adjudicated)	ATTR-CM defined by biopsy or imaging-based diagnosis; ATTR-PN defined by new signs or symptoms and biopsy-based diagnosis	Since randomization up to approximately 7 years or until the study is declared over

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to development of ATTR-CM (centrally adjudicated)	ATTR-CM defined by biopsy or imaging-based diagnosis	Since randomization up to approximately 7 years or until the study is declared over
Time to development of ATTR-PN (centrally adjudicated)	ATTR-PN defined by new signs or symptoms and biopsy-based diagnosis	Since randomization up to approximately 7 years or until the study is declared over

Collaborators and Investigators

• Sponsor: Eidos Therapeutics, a BridgeBio company

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2025
• Primary Completion (Estimated): October 1, 2031
• Study Completion (Estimated): December 1, 2032

Study Registration Dates

• First Submitted: August 5, 2024
• First Submitted That Met QC Criteria: August 18, 2024
• First Posted (Actual): August 21, 2024

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 8, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: TTR; Amyloidosis; Transthyretin; Amyloid; ATTR-CM; ATTR-PN
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cardiovascular Diseases; Mental Disorders; Neuromuscular Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Peripheral Nervous System Diseases; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Proteostasis Deficiencies; Amyloid Neuropathies; Amyloidosis, Familial; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Alzheimer Disease; Heart Diseases; Polyneuropathies; Cardiomyopathies; Amyloidosis; Amyloid Neuropathies, Familial; Amyloidosis, Hereditary, Transthyretin-Related; attruby
• Other Study ID Numbers: AG10-501; U1111-1307-8107 (Other Identifier: WHO); jRCT2071250116 (Other Identifier: Japan Registry of Clinical Trials)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No