Clinical trial NCT04988386: Open-Label Safety Study of Acoramidis (AG10) in Symptomatic ATTR Participants
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Amyloid Cardiomyopathy, Transthyretin-Related
Keywords: ATTR-CM
Lead sponsor: Eidos Therapeutics, a BridgeBio company
Sponsor class: INDUSTRY
First posted: 2021-08-03
Enrollment: 389
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open-label study extension study from the AG10-301 double-blind study.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of treatment-emergent Adverse Events [Safety and Tolerability]
timeFrame: 60 months
Secondary outcomes:
measure: Evaluate all-cause mortality and cardiovascular mortality
timeFrame: 60 months
measure: Evaluate the effect of acoramidis on the 6-minute walk test (6MWT)
timeFrame: 60 months
measure: Evaluate the effect of acoramidis on health-related quality of life Kansas City Cardiomyopathy Questionnaire
timeFrame: 60 months
measure: Evaluate the effect of acoramidis on the frequency of CV-related hospitalization
timeFrame: 60 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Medical Campus
state: Colorado
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Evanston
country: United States
facility: NorthShore University Health System
state: Illinois
city: Baltimore
country: United States
facility: MedStar Medical Group Cardiology at Franklin Square
state: Maryland
city: Boston
country: United States
facility: Boston University Medical Center General Clinical Research Unit
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Bronx
country: United States
facility: Montefiore Medical Center at Hutchinson
state: New York
city: New York
country: United States
facility: New York University Langone Health
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: Rosedale
country: United States
facility: Laurelton Heart Specialists
state: New York
city: Durham
country: United States
facility: Duke University Health System - Duke Clinic
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Main Campus
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: Penn Presbyterian Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center (UPMC)
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth University Health System
state: Virginia
city: Roanoke
country: United States
facility: Roanoke Heart Institute
state: Virginia
city: Seattle
country: United States
facility: University of Washington School of Medicine
state: Washington
city: Spokane
country: United States
facility: Providence Sacred Heart Children's Hospital
state: Washington
city: Darlinghurst
country: Australia
facility: Saint Vincent's Hospital Sydney
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Genk
country: Belgium
facility: Ziekenhuis Oost-Limburg
state: Limburg
city: Brugge
country: Belgium
facility: Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan
state: West Vlaanderen
city: Porto Alegre
country: Brazil
facility: Instituto de Cardiologia do Rio Grande do Sul
state: Rio Grande do Sul
city: Ribeirão Preto
country: Brazil
facility: Centro Avançado de Pesquisa e Estudos para o Diagnóstico CAPED
state: Sao Paulo
city: São Paulo
country: Brazil
facility: Instituto do Coração de São Paulo
state: Sao Paulo
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: Saint Boniface Hospital
state: Manitoba
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre - Halifax Infirmary
state: Nova Scotia
city: Toronto
country: Canada
facility: Toronto Heart Centre
state: Ontario
city: Montréal
country: Canada
facility: L' Institut de Cardiologie de Montréal
state: Quebec
city: Montréal
country: Canada
facility: Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CHUM)
state: Quebec
city: Montréal
country: Canada
facility: Hôpital du Sacré-Coeur de Montréal
state: Quebec
city: Rimouski
country: Canada
facility: Hôpital régional de Rimouski
state: Quebec
city: Praha 2
country: Czechia
facility: Vseobecna Fakultni Nemocnice v Praze
state: Prague
city: Praha 4
country: Czechia
facility: Institut Klinické a Experimentální Medicíny
state: Prague
city: Brno
country: Czechia
facility: Fakultní Nemocnice u sv. Anny v Brně
state: South Moravian
city: Aarhus N
country: Denmark
facility: Aarhus Universitets Hospital
state: Palle Juul-Jensens
city: Athens
country: Greece
facility: Alexandra General Hospital of Athens
state: Attica
city: Dublin
country: Ireland
facility: Mater Misericordiae University Hospital
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center
state: Tel Aviv
city: Jerusalem
country: Israel
facility: Hadassah University Hospital Ein Kerem
city: Firenze
country: Italy
facility: Azienda Ospedaliero - Universitaria Careggi
state: Florence
city: Arezzo
country: Italy
facility: Ospedale San Donato
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Pisa
country: Italy
facility: Fondazione Toscana Gabriele Monasterio per la Ricerca Medica e di Sanità Pubblica
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-Do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Gyeonggi-Do
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Papatoetoe
country: New Zealand
facility: Middlemore Clinical Trials - Middlemore Hospital
state: Auckland
city: Hamilton
country: New Zealand
facility: Waikato Hospital
state: Waikato
city: Lisbon
country: Portugal
facility: Centro Hospitalar Universitário Lisboa Norte EPE- Hospital Santa Maria
state: Lisboa
city: Palma De Mallorca
country: Spain
facility: Hospital Son Llàtzer
state: Balearic Islands
city: Santiago De Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago (CHUS)
state: La Coruña
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro - Majadahonda
state: Madrid
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra
state: Navarra
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra Madrid
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: London
country: United Kingdom
facility: National Amyloidosis Centre, Division of Medicine - Royal Free
state: England
city: London
country: United Kingdom
facility: Richmond Pharmacology Ltd
state: England
Study officials:
References: