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

Amyloid Cardiomyopathy, Transthyretin-Related Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04988386
• Other study ID #: AG10-304
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 27, 2021
• Est. completion date: May 15, 2028

Study information

• Verified date: September 2023
• Source: Eidos Therapeutics, a BridgeBio company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Description:

The primary objective of this prospective multi-center, open-label study is to evaluate the long-term safety and tolerability of acoramidis in the context of background heart failure therapy. Selected secondary efficacy endpoints and exploratory pharmacokinetic, pharmacodynamic/biomarker endpoints 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 day as the Month 30 visit in Study AG10-301. Under these circumstances, the last dose of Investigational Medicinal Product (IMP) in Study AG10-301 will be the night before the day of the Month 30 visit and the first dose of 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 treatments, or therapies used off-label or as non-prescription supplements for ATTR-CM at any time during the study. If participants choose treatment with a prohibited medication, they may be asked to discontinue acoramidis and they may be asked to discontinue/withdraw from the study. Under these circumstances, participants will be asked to complete an early termination visit, and a follow-up visit prior to discontinuation/withdrawal.

Participants are not permitted to participate in another interventional clinical trial (with the exception of Study AG10-301) within 30 days prior to dosing and throughout Study AG10-304. Participants who choose to participate in another interventional clinical trial may be asked to withdraw from acoramidis and/or the study. In such cases, participants will be asked to complete an early termination visit and a follow-up visit. Participation in observational and/or registry studies should be discussed with the Medical Monitor.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 389
• Est. completion date: May 15, 2028
• Est. primary completion date: April 15, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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.

Related Conditions & MeSH terms

• Amyloid Cardiomyopathy, Transthyretin-Related
• Amyloidosis
• Cardiomyopathies

Intervention

Drug:
• Acoramidis (AG10)
Acoramidis (AG10) twice daily

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	Saint Vincent's Hospital Sydney	Darlinghurst	New South Wales
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	Fiona Stanley Hospital	Murdoch	Western Australia
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Belgium	Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan	Brugge	West Vlaanderen
Belgium	Ziekenhuis Oost-Limburg	Genk	Limburg
Brazil	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
Canada	Queen Elizabeth II Health Sciences Centre - Halifax Infirmary	Halifax	Nova Scotia
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	L' Institut de Cardiologie de Montréal	Montréal	Quebec
Canada	Hôpital régional de Rimouski	Rimouski	Quebec
Canada	Toronto Heart Centre	Toronto	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia
Canada	Saint Boniface Hospital	Winnipeg	Manitoba
Czechia	Fakultní Nemocnice u sv. Anny v Brne	Brno	South Moravian
Czechia	Vseobecna Fakultni Nemocnice v Praze	Praha 2	Prague
Czechia	Institut Klinické a Experimentální Medicíny	Praha 4	Prague
Denmark	Aarhus Universitets Hospital	Aarhus N	Palle Juul-Jensens
Greece	Alexandra General Hospital of Athens	Athens	Attica
Ireland	Mater Misericordiae University Hospital	Dublin
Israel	Hadassah University Hospital Ein Kerem	Jerusalem
Israel	The Chaim Sheba Medical Center	Ramat Gan	Tel Aviv
Italy	Ospedale San Donato	Arezzo
Italy	Azienda Ospedaliero - Universitaria Careggi	Firenze	Florence
Italy	Fondazione IRCCS Policlinico San Matteo	Pavia
Italy	Fondazione Toscana Gabriele Monasterio per la Ricerca Medica e di Sanità Pubblica	Pisa
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-Do
Korea, Republic of	Seoul National University Hospital	Seoul	Gyeonggi-Do
Netherlands	Universitair Medisch Centrum Groningen	Groningen
Netherlands	Universitair Medisch Centrum Utrecht	Utrecht
New Zealand	Waikato Hospital	Hamilton	Waikato
New Zealand	Middlemore Clinical Trials - Middlemore Hospital	Papatoetoe	Auckland
Portugal	Centro Hospitalar Universitário Lisboa Norte EPE- Hospital Santa Maria	Lisbon	Lisboa
Spain	Clinica Universidad de Navarra Madrid	Madrid
Spain	Hospital Universitario Puerta de Hierro - Majadahonda	Majadahonda	Madrid
Spain	Hospital Son Llàtzer	Palma De Mallorca	Balearic Islands
Spain	Clínica Universidad de Navarra	Pamplona	Navarra
Spain	Complejo Hospitalario Universitario de Santiago (CHUS)	Santiago De Compostela	La Coruña
Spain	Hospital Clínico Universitario de Valencia	Valencia
United Kingdom	National Amyloidosis Centre, Division of Medicine - Royal Free	London	England
United Kingdom	Richmond Pharmacology Ltd	London	England
United States	University of Colorado Hospital - Anschutz Medical Campus	Aurora	Colorado
United States	MedStar Medical Group Cardiology at Franklin Square	Baltimore	Maryland
United States	Boston University Medical Center General Clinical Research Unit	Boston	Massachusetts
United States	Montefiore Medical Center at Hutchinson	Bronx	New York
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Cleveland Clinic Main Campus	Cleveland	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Duke University Health System - Duke Clinic	Durham	North Carolina
United States	NorthShore University Health System	Evanston	Illinois
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Columbia University Irving Medical Center	New York	New York
United States	New York University Langone Health	New York	New York
United States	Penn Presbyterian Medical Center	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center (UPMC)	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	Virginia Commonwealth University Health System	Richmond	Virginia
United States	Roanoke Heart Institute	Roanoke	Virginia
United States	Mayo Clinic - Rochester	Rochester	Minnesota
United States	Laurelton Heart Specialists	Rosedale	New York
United States	Washington University	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah
United States	University of Washington School of Medicine	Seattle	Washington
United States	Providence Sacred Heart Children's Hospital	Spokane	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Eidos Therapeutics, a BridgeBio company

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Canada,  Czechia,  Denmark,  Greece,  Ireland,  Israel,  Italy,  Korea, Republic of,  Netherlands,  New Zealand,  Portugal,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Evaluate all-cause mortality and cardiovascular mortality	Assessment of All-cause mortality and CV mortality during study period	60 months
Secondary	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
Secondary	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
Secondary	Evaluate the effect of acoramidis on the frequency of CV-related hospitalization	assess CV-related hospitalization during the study period	60 months