Open-Label Safety Study of Acoramidis (AG10) in Symptomatic ATTR Participants (AG10)

An Open-Label Extension and Safety Monitoring Study of Acoramidis (AG10) in Participants With Symptomatic Transthyretin Amyloid Cardiomyopathy Who Completed the Phase 3 ATTRibute-CM Trial (AG10-301)

Open-Label Extension and Safety Monitoring Study of Acoramidis (AG10) in Participants with Symptomatic Transthyretin Amyloid Cardiomyopathy Who Completed the Phase 3 ATTRibute-CM Trial (AG10-301)

Study Overview

• Status: Active, not recruiting
• Conditions: Amyloid Cardiomyopathy, Transthyretin-Related
• Intervention / Treatment: Drug: Acoramidis (AG10)

Detailed Description

The primary objective of this prospective, multi-center, open-label study is to evaluate the long-term safety and tolerability of acoramidis in patients with an established diagnosis of ATTR-CM and heart failure who are concomitantly treated with currently recommended heart failure therapies. Secondary efficacy and PD objectives will be assessed. Exploratory objectives may also be assessed.

All participants who complete 30 months of blinded study treatment and the Month 30 assessments of the double-blind treatment period of the Phase 3 ATTRibute-CM trial (AG10-301) may be eligible to participate in this Open Label Extension (OLE) study of acoramidis. The Day 1 visit in Study AG10-304 may be the same as the Month 30 visit in Study AG10-301. Under these circumstances, the last dose of Investigational Medicinal Product (IMP) in Study AG10-301 (either blinded acoramidis or matching placebo) will be the night before the day of the Month 30 visit. The first dose of open-label acoramidis in Study AG10-304 will be during the Study AG10-304 Day 1 visit after baseline assessments have been completed.

Currently, tafamidis is approved for the treatment of ATTR-CM in some regions. Participants are not allowed to be treated with tafamidis or any other ATTR-CM-specific approved or investigational treatment, or therapies used off-label or as non-prescription supplements for ATTR-CM at any time during the study. If participants choose treatment with an alternative treatment as described above, they will be asked to discontinue acoramidis and complete an End of Treatment (EoT) form, and they may be asked to discontinue/withdraw from the study. If a participant discontinues/withdraws from the study, the participant will be asked to complete an early termination visit and a safety follow-up visit.

Participants are not permitted to participate in another interventional clinical trial (except Study AG10-301) within 30 days prior to dosing and throughout Study AG10-304. Participants who choose to participate in another interventional clinical trial will be asked to withdraw from acoramidis and complete an EoT form, and they may be asked to discontinue/withdraw from the study. If a participant discontinues/withdraws from the study, the participant will be asked to complete an early termination visit and a safety follow-up visit. Participation in observational and/or registry studies should be discussed with the Medical Monitor.

• Study Type: Interventional
• Enrollment (Actual): 389
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Saint Vincent's Hospital Sydney
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Royal Hobart Hospital
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Box Hill Hospital
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital
• Belgium
  • Limburg
    • Genk, Limburg, Belgium, 3600
      • Ziekenhuis Oost-Limburg
  • West Vlaanderen
    • Bruges, West Vlaanderen, Belgium, 8000
      • Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan
• Brazil
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90620-001
      • Instituto de Cardiologia do Rio Grande do Sul
  • São Paulo
    • Ribeirão Preto, São Paulo, Brazil, 14026-900
      • Centro Avançado de Pesquisa e Estudos para o Diagnóstico CAPED
    • São Paulo, São Paulo, Brazil, 05403-000
      • Instituto do Coração de São Paulo
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver General Hospital
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H 2A6
      • Saint Boniface Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 3A7
      • Queen Elizabeth II Health Sciences Centre - Halifax Infirmary
  • Ontario
    • Toronto, Ontario, Canada, M4P IE4
      • Toronto Heart Centre
  • Quebec
    • Montreal, Quebec, Canada, H4J 1C5
      • Hopital Du Sacre-Coeur de Montreal
    • Montreal, Quebec, Canada, H1T 1C8
      • L' Institut de Cardiologie de Montréal
    • Montreal, Quebec, Canada, H2X 0A9
      • Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CHUM)
    • Rimouski, Quebec, Canada, G5L 5T1
      • Hôpital Regional de Rimouski
• Czechia
  • Prague
    • Prague, Prague, Czechia, 140 21
      • Institut klinicke a experimentalni mediciny
    • Prague, Prague, Czechia, 128 08
      • Všeobecná fakultní nemocnice v Praze
  • South Moravian
    • Brno, South Moravian, Czechia, 656 91
      • Fakultni nemocnice u sv. Anny v Brne
• Denmark
  • Palle Juul-Jensens
    • Aarhus N, Palle Juul-Jensens, Denmark, 8200
      • Aarhus Universitets Hospital
• Greece
  • Attica
    • Athens, Attica, Greece, 11528
      • Alexandra General Hospital of Athens
• Ireland
  • Dublin
    • Dublin, Dublin, Ireland, 7
      • Mater Misericordiae University Hospital
• Israel
  • Jerusalem, Israel, 9112001
    • Hadassah University Hospital Ein Kerem
  • Tel Aviv
    • Ramat Gan, Tel Aviv, Israel, 5265601
      • The Chaim Sheba Medical Center
• Italy
  • Pavia, Italy, 27100
    • Fondazione IRCCS Policlinico San Matteo
  • Arezzo
    • Arezzo, Arezzo, Italy, 52100
      • Ospedale San Donato
  • Florence
    • Florence, Florence, Italy, 50134
      • Azienda Ospedaliero - Universitaria Careggi
  • Pisa
    • Pisa, Pisa, Italy, 56124
      • Fondazione Toscana Gabriele Monasterio per la Ricerca Medica e di Sanita Pubblica
• Netherlands
  • Provincie Groningen
    • Groningen, Provincie Groningen, Netherlands, 9713 GZ
      • Universitair Medisch Centrum Groningen
  • Utrecht
    • Utrecht, Utrecht, Netherlands, 3584 CX
      • Universitair Medisch Centrum Utrecht
• New Zealand
  • Auckland
    • Papatoetoe, Auckland, New Zealand, 2025
      • Middlemore Clinical Trials - Middlemore Hospital
  • Waikato Region
    • Hamilton, Waikato Region, New Zealand, 3240
      • Waikato Hospital
• Portugal
  • Lisbon District
    • Lisbon, Lisbon District, Portugal, 1649-035
      • Centro Hospitalar Universitário Lisboa Norte EPE- Hospital Santa Maria
• South Korea
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, South Korea, 13620
      • Seoul National University Bundang Hospital
    • Seoul, Gyeonggi-do, South Korea, 3080
      • Seoul National University Hospital
• Spain
  • Balearic Islands
    • Palma de Mallorca, Balearic Islands, Spain, 7198
      • Hospital Son Llatzer
  • La Coruña
    • Santiago de Compostela, La Coruña, Spain, 15706
      • Complejo Hospitalario Universitario de Santiago (CHUS)
  • Madrid
    • Madrid, Madrid, Spain, 28027
      • Clinica Universidad de Navarra Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro - Majadahonda
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Clinica Universidad de Navarra
  • Valencia
    • Valencia, Valencia, Spain, 46010
      • Hospital Clínico Universitario de Valencia
• United Kingdom
  • England
    • London, England, United Kingdom, NW3 2PF
      • National Amyloidosis Centre, Division of Medicine - Royal Free
    • London, England, United Kingdom, SE1 1YR
      • Richmond Pharmacology Ltd
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital - Anschutz Medical Campus
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
    • Evanston, Illinois, United States, 60201
      • NorthShore University Health System
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • MedStar Medical Group Cardiology at Franklin Square
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston University Medical Center General Clinical Research Unit
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic - Rochester
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Hospital of Kansas City
    • St Louis, Missouri, United States, 63110
      • Washington University
  • New York
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center
    • New York, New York, United States, 10016
      • New York University Langone Health
    • Rosedale, New York, United States, 11422
      • Laurelton Heart Specialists
    • The Bronx, New York, United States, 10461
      • Montefiore Medical Center at Hutchinson
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Health System - Duke Clinic
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Main Campus
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Presbyterian Medical Center
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center (UPMC)
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Virginia Commonwealth University Health System
    • Roanoke, Virginia, United States, 24014
      • Roanoke Heart Institute
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington School of Medicine
    • Spokane, Washington, United States, 99204
      • Providence Sacred Heart Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Completed 30 months of the blinded study treatment in Study AG10-301 and the Study AG10-301 Month 30 visit including assessments and procedures.
2. Have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures.
3. Female participants of childbearing potential who engage in heterosexual intercourse must agree to use a highly effective method of contraception beginning with enrollment and continuing for 30 days after the last dose of acoramidis. Female participants using oral contraceptives must agree to use an additional birth control method. While not considered highly effective, a double-barrier method is acceptable. A male participant who is sexually active with a female of childbearing potential and has not had a vasectomy must agree to use a double-barrier method of birth control.

Exclusion Criteria:

1. Acute myocardial infarction, acute coronary syndrome or coronary revascularization within 90 days prior to Day 1 stroke or transient ischemic attack (TIA) within 90 days prior to Day 1.
2. Has hemodynamic instability, that in the judgment of the Investigator, would pose too great a risk for participation in the study.
3. Has had a heart and/or liver transplant or is on the heart transplantation list within the year prior to Day 1
4. Has had implantation of a cardiac mechanical assist device (CMAD) or is scheduled for implantation of a CMAD
5. Has confirmed diagnosis of light-chain (AL) amyloidosis at any time during Study AG10-301.
6. Has estimated glomerular filtration rate (eGFR) by modification of diet for renal disease (MDRD) formula < 15 mL/min/1.73 m2 at Month 27 of Study AG10-301 or at any subsequent central lab value prior to Day 1.
7. Known hypersensitivity to acoramidis, its metabolites, or formulation excipients.
8. At the end of Study AG10-301 or at Day 1 of Study AG10-304 (or any time during the study), participant is on prohibited medication.
9. Females who are pregnant or breastfeeding. A negative urine pregnancy test at the Day 1 visit and at each study visit are required for female participants of childbearing potential.
10. In the judgment of the Investigator or Medical Monitor, has any clinically important ongoing medical condition or laboratory abnormality or condition that might jeopardize the participant's safety, increase their risk from participation, or interfere with the study.
11. Participation in another interventional clinical trial (with the exception of Study AG10-301) within 30 days prior to dosing. Participation in observational and/or registry studies should be discussed with the Medical Monitor.
12. Has any condition that in the opinion of the Investigator or Medical Monitor would preclude compliance with the study protocol such as a history of substance abuse, alcoholism, or a psychiatric condition.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AG10; Open-label study all participants will receive AG10 during this study.	Drug: Acoramidis (AG10); Acoramidis (AG10) twice daily; Other Names: AG10; ALXN 2060

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-emergent Adverse Events [Safety and Tolerability]	Incidence of each treatment-emergent adverse events measured over 60 Months or study completion	60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate all-cause mortality and cardiovascular mortality	Assessment of All-cause mortality and CV mortality during study period	60 months
Evaluate the effect of acoramidis on the 6-minute walk test (6MWT)	Change from Baseline in distance walked during the 6MWT during study period	60 months
Evaluate the effect of acoramidis on health-related quality of life Kansas City Cardiomyopathy Questionnaire	Change from Baseline in Kansas City Cardiomyopathy Questionnaire Overall Score during study period [scale is scored from 0-100, where 0=Poor, 100=Excellent]	60 months
Evaluate the effect of acoramidis on the frequency of CV-related hospitalization	assess CV-related hospitalization during the study period	60 months

Collaborators and Investigators

• Sponsor: Eidos Therapeutics, a BridgeBio company

Publications and helpful links

General Publications

• Judge DP, Gillmore JD, Alexander KM, Ambardekar AV, Cappelli F, Fontana M, Garcia-Pavia P, Grodin JL, Grogan M, Hanna M, Masri A, Nativi-Nicolau J, Obici L, Hvitfeldt Poulsen S, Sarswat N, Shah K, Soman P, Lystig T, Cao X, Wang K, Pecoraro ML, Tamby JF, Katz L, Sinha U, Fox JC, Maurer MS. Long-Term Efficacy and Safety of Acoramidis in ATTR-CM: Initial Report From the Open-Label Extension of the ATTRibute-CM Trial. Circulation. 2025 Mar 4;151(9):601-611. doi: 10.1161/CIRCULATIONAHA.124.072771. Epub 2024 Nov 18.

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2021
• Primary Completion (Estimated): April 15, 2028
• Study Completion (Estimated): May 15, 2028

Study Registration Dates

• First Submitted: July 13, 2021
• First Submitted That Met QC Criteria: July 30, 2021
• First Posted (Actual): August 3, 2021

Study Record Updates

• Last Update Posted (Estimated): October 14, 2025
• Last Update Submitted That Met QC Criteria: October 9, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: ATTR-CM
• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Peripheral Nervous System Diseases; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Proteostasis Deficiencies; Amyloid Neuropathies; Amyloidosis, Familial; Amyloidosis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Amyloid Neuropathies, Familial; attruby
• Other Study ID Numbers: AG10-304; 2020-005643-22 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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