Acoramidis Transthyretin Amyloidosis Prevention Trial in the Young (ACT-EARLY) Study in Asymptomatic Carriers of a Pathogenic TTR Variant
- Conditions
- CardiomyopathiesPolyneuropathiesAmyloidosisTransthyretin AmyloidosisAmyloid CardiomyopathyHeart Diseases
- Interventions
- Drug: Placebo oral tablet
- Registration Number
- NCT06563895
- Lead Sponsor
- Eidos Therapeutics, a BridgeBio company
- Brief Summary
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.
- 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 no more than 10 years younger 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 40 and 75 years inclusive.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 582
- Male or female ≥ 18 to ≤ 75 years of age inclusive.
- Participants must have an established genotype (hetero- or homozygosity) of a TTR gene variant that is known to be pathogenic (eg, V30M/p.V50M, V122I/p.V142I, T60A/p.T80A, or any other pathogenic TTR variant(s)) confirmed by central laboratory prior to randomization.
- Participant's age is no more than 10 years (≤ 10) younger than the PADO.
Key
- Evidence of ATTR-CM or ATTR-PN.
- Presence of a TTR variant known to be phenotypically protective (eg, T119M, R104H).
- Current or past 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 3 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description acoramidis Acoramidis Participants will receive acoramidis 712 mg orally BID (which is equivalent to 800 mg acoramidis HCl BID) Placebo Placebo oral tablet Subjects will receive placebo to match twice daily
- Primary Outcome Measures
Name Time Method Time to development of ATTR (ATTR-CM or ATTR-PN, whichever occurs first; centrally adjudicated) Since randomization up to approximately 7 years or until the study is declared over * ATTR-CM defined by biopsy or imaging-based diagnosis
* ATTR-PN defined by new signs or symptoms and biopsy-based diagnosis
- Secondary Outcome Measures
Name Time Method Time to development of ATTR-CM (centrally adjudicated) Since randomization up to approximately 7 years or until the study is declared over ATTR-CM defined by biopsy or imaging-based diagnosis
Time to development of ATTR-PN (centrally adjudicated) Since randomization up to approximately 7 years or until the study is declared over ATTR-PN defined by new signs or symptoms and biopsy-based diagnosis
Trial Locations
- Locations (22)
Hospital Universitario Puerta de Hierro
🇪🇸Majadahonda, Spain
Yale University School of Medicine - Section of Cardiology
🇺🇸New Haven, Connecticut, United States
Mayo Clinic - Jacksonville
🇺🇸Jacksonville, Florida, United States
Emory University School of Medicine
🇺🇸Atlanta, Georgia, United States
University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Mayo Clinic - Rochester
🇺🇸Rochester, Minnesota, United States
New York University (NYU) School of Medicine - Langone Medical Center
🇺🇸New York, New York, United States
Fondazione Toscana Gabriele Monasterio per la Ricerca Medica e di Sanità Pubblica - Ospedale San Cataldo
🇮🇹Pisa, Italy
Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore
🇮🇹Rome, Italy
Universitair Medisch Centrum Utrecht
🇳🇱Utrecht, Netherlands
Stanford University
🇺🇸Stanford, California, United States
MedStar Washington Hospital Center - MedStar Heart and Vascular Institute
🇺🇸Washington, District of Columbia, United States
John H. Stroger, Jr. Hospital of Cook County
🇺🇸Chicago, Illinois, United States
St. Luke's Hospital of Kansas City
🇺🇸Kansas City, Missouri, United States
Rutgers-Robert Wood Johnson Medical School
🇺🇸New Brunswick, New Jersey, United States
Medical University of South Carolina (MUSC)
🇺🇸Charleston, South Carolina, United States
Prisma Health Cancer Institute
🇺🇸Greenville, South Carolina, United States
National Neuromuscular Research Institute
🇺🇸Austin, Texas, United States
UMHAT Aleksandrovska Sofia, Clinic of Neurology Diseases
🇧🇬Sofia, Bulgaria
Azienda Ospedaliero-Universitaria Careggi
🇮🇹Florence, Italy
Hospital Universitario Juan Ramon Jimenez
🇪🇸Huelva, Spain