Acoramidis Transthyretin Amyloidosis Prevention Trial in the Young (ACT-EARLY) Study in Asymptomatic Carriers of a Pathogenic TTR Variant

Eidos Therapeutics

Status and phase: Enrolling; Phase 3

Conditions: Transthyretin Amyloidosis; Polyneuropathies; Amyloid Cardiomyopathy; Amyloidosis; Heart Diseases; Cardiomyopathies

Treatments: Drug: Placebo oral tablet; Drug: Acoramidis

Study type: Interventional

Funder types: Industry

Identifiers

NCT06563895

AG10-501

Details and patient eligibility

About

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.

Full 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 between 40 and 75 years inclusive.

Enrollment: 582 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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 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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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582 participants in 2 patient groups, including a placebo group

acoramidis

Experimental group

Description:

Participants will receive acoramidis 712 mg orally BID (which is equivalent to 800 mg acoramidis HCl BID)

Treatment:

Drug: Acoramidis

Placebo

Placebo Comparator group

Description:

Subjects will receive placebo to match twice daily

Treatment:

Drug: Placebo oral tablet