A Phase 3, Randomized, Multicenter, Double-Blind, Placebo-Controlled Study of Acoramidis for Transthyretin Amyloidosis Prevention in the Young (ACT-EARLY Trial)
Eidos Therapeutics, a BridgeBio company
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.
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 fa…
Eligibility
- Age range
- 18–75 years
- Sex
- All
- Healthy volunteers
- No
Key Inclusion Criteria: * 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 Exclusion Criteria: * Evidence of ATTR-CM or ATTR-PN. * Presence of a TTR variant known to be phenotypically protective (eg, T119M, R104H). * Current or past treatment wi…
Interventions
- DrugAcoramidis
TTR stabilizer administered orally twice daily (BID)
- DrugPlacebo oral tablet
Non-active control administered orally twice daily (BID)
Locations (98)
- University of California, San Diego (UCSD) - Medical CenterLa Jolla, California
- University of California, Los Angeles (UCLA) - David Geffen School of MedicineLos Angeles, California
- University of California, San Francisco (UCSF)San Francisco, California
- Stanford UniversityStanford, California
- University of Colorado AnschutzAurora, Colorado
- Yale University School of Medicine - Section of CardiologyNew Haven, Connecticut