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

Phase 3

Active, not recruiting

• Conditions: Amyloid Cardiomyopathy, Transthyretin-Related
• Interventions: Drug: Acoramidis (AG10)

• Registration Number: NCT04988386
• Lead Sponsor: Eidos Therapeutics, a BridgeBio company

Brief Summary

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)

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 Timeline

• Study First Submitted: 2021-07-13
• Study First Submitted QC: 2021-07-30
• Study First Posted: 2021-08-03
• Study Start: 2021-10-27
• Status Verified: 2025-02
• Last Update Submitted: 2025-03-25
• Last Update Posted: 2025-03-30
• Primary Completion: 2028-04-15
• Study Completion: 2028-05-15

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 389

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
AG10	Acoramidis (AG10)	Open-label study all participants will receive AG10 during this study.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (72)

Cedars-Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

University of Colorado Hospital - Anschutz Medical Campus; 🇺🇸 Aurora, Colorado, United States

University of Chicago Medical Center; 🇺🇸 Chicago, Illinois, United States

NorthShore University Health System; 🇺🇸 Evanston, Illinois, United States

Boston University Medical Center General Clinical Research Unit; 🇺🇸 Boston, Massachusetts, United States

Mayo Clinic - Rochester; 🇺🇸 Rochester, Minnesota, United States

Washington University; 🇺🇸 Saint Louis, Missouri, United States

Montefiore Medical Center at Hutchinson; 🇺🇸 Bronx, New York, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

MedStar Medical Group Cardiology at Franklin Square; 🇺🇸 Baltimore, Maryland, United States

Saint Luke's Hospital of Kansas City; 🇺🇸 Kansas City, Missouri, United States

New York University Langone Health; 🇺🇸 New York, New York, United States

Columbia University Irving Medical Center; 🇺🇸 New York, New York, United States

Laurelton Heart Specialists; 🇺🇸 Rosedale, New York, United States

Duke University Health System - Duke Clinic; 🇺🇸 Durham, North Carolina, United States

Cleveland Clinic Main Campus; 🇺🇸 Cleveland, Ohio, United States

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States

University of Pittsburgh Medical Center (UPMC); 🇺🇸 Pittsburgh, Pennsylvania, United States

Penn Presbyterian Medical Center; 🇺🇸 Philadelphia, Pennsylvania, United States

Medical University of South Carolina; 🇺🇸 Charleston, 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 Health System; 🇺🇸 Richmond, Virginia, United States

Roanoke Heart Institute; 🇺🇸 Roanoke, Virginia, United States

University of Washington School of Medicine; 🇺🇸 Seattle, Washington, United States

Providence Sacred Heart Children's Hospital; 🇺🇸 Spokane, Washington, United States

Saint Vincent's Hospital Sydney; 🇦🇺 Darlinghurst, New South Wales, Australia

Princess Alexandra Hospital; 🇦🇺 Woolloongabba, Queensland, Australia

Royal Adelaide Hospital; 🇦🇺 Adelaide, South Australia, Australia

Royal Hobart Hospital; 🇦🇺 Hobart, Tasmania, Australia

Box Hill Hospital; 🇦🇺 Box Hill, Victoria, Australia

Fiona Stanley Hospital; 🇦🇺 Murdoch, Western Australia, Australia

Ziekenhuis Oost-Limburg; 🇧🇪 Genk, Limburg, Belgium

Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan; 🇧🇪 Brugge, West Vlaanderen, Belgium

Instituto de Cardiologia do Rio Grande do Sul; 🇧🇷 Porto Alegre, Rio Grande do Sul, Brazil

Centro Avançado de Pesquisa e Estudos para o Diagnóstico CAPED; 🇧🇷 Ribeirão Preto, Sao Paulo, Brazil

Instituto do Coração de São Paulo; 🇧🇷 São Paulo, Sao Paulo, Brazil

Vancouver General Hospital; 🇨🇦 Vancouver, British Columbia, Canada

Saint Boniface Hospital; 🇨🇦 Winnipeg, Manitoba, Canada

Queen Elizabeth II Health Sciences Centre - Halifax Infirmary; 🇨🇦 Halifax, Nova Scotia, Canada

Toronto Heart Centre; 🇨🇦 Toronto, Ontario, Canada

L' Institut de Cardiologie de Montréal; 🇨🇦 Montréal, Quebec, Canada

Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CHUM); 🇨🇦 Montréal, Quebec, Canada

Hôpital du Sacré-Coeur de Montréal; 🇨🇦 Montréal, Quebec, Canada

Hôpital régional de Rimouski; 🇨🇦 Rimouski, Quebec, Canada

Vseobecna Fakultni Nemocnice v Praze; 🇨🇿 Praha 2, Prague, Czechia

Institut Klinické a Experimentální Medicíny; 🇨🇿 Praha 4, Prague, Czechia

Fakultní Nemocnice u sv. Anny v Brně; 🇨🇿 Brno, South Moravian, Czechia

Aarhus Universitets Hospital; 🇩🇰 Aarhus N, Palle Juul-Jensens, Denmark

Alexandra General Hospital of Athens; 🇬🇷 Athens, Attica, Greece

Mater Misericordiae University Hospital; 🇮🇪 Dublin, Ireland

The Chaim Sheba Medical Center; 🇮🇱 Ramat Gan, Tel Aviv, Israel

Hadassah University Hospital Ein Kerem; 🇮🇱 Jerusalem, Israel

Azienda Ospedaliero - Universitaria Careggi; 🇮🇹 Firenze, Florence, Italy

Ospedale San Donato; 🇮🇹 Arezzo, Italy

Fondazione IRCCS Policlinico San Matteo; 🇮🇹 Pavia, Italy

Fondazione Toscana Gabriele Monasterio per la Ricerca Medica e di Sanità Pubblica; 🇮🇹 Pisa, Italy

Seoul National University Bundang Hospital; 🇰🇷 Seongnam-si, Gyeonggi-Do, Korea, Republic of

Seoul National University Hospital; 🇰🇷 Seoul, Gyeonggi-Do, Korea, Republic of

Universitair Medisch Centrum Groningen; 🇳🇱 Groningen, Netherlands

Universitair Medisch Centrum Utrecht; 🇳🇱 Utrecht, Netherlands

Middlemore Clinical Trials - Middlemore Hospital; 🇳🇿 Papatoetoe, Auckland, New Zealand

Waikato Hospital; 🇳🇿 Hamilton, Waikato, New Zealand

Centro Hospitalar Universitário Lisboa Norte EPE- Hospital Santa Maria; 🇵🇹 Lisbon, Lisboa, Portugal

Hospital Son Llàtzer; 🇪🇸 Palma De Mallorca, Balearic Islands, Spain

Complejo Hospitalario Universitario de Santiago (CHUS); 🇪🇸 Santiago De Compostela, La Coruña, Spain

Hospital Universitario Puerta de Hierro - Majadahonda; 🇪🇸 Majadahonda, Madrid, Spain

Clínica Universidad de Navarra; 🇪🇸 Pamplona, Navarra, Spain

Clinica Universidad de Navarra Madrid; 🇪🇸 Madrid, Spain

Hospital Clínico Universitario de Valencia; 🇪🇸 Valencia, Spain

National Amyloidosis Centre, Division of Medicine - Royal Free; 🇬🇧 London, England, United Kingdom

Richmond Pharmacology Ltd; 🇬🇧 London, England, United Kingdom