Clinical trial NCT06563895: Acoramidis Transthyretin Amyloidosis Prevention Trial in the Young (ACT-EARLY) Study in Asymptomatic Carriers of a Pathogenic TTR Variant
Official title: A Phase 3, Randomized, Multicenter, Double-Blind, Placebo-Controlled Study of Acoramidis for Transthyretin Amyloidosis Prevention in the Young (ACT-EARLY Trial)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Amyloidosis
Amyloid Cardiomyopathy
Transthyretin Amyloidosis
Cardiomyopathies
Heart Diseases
Polyneuropathies
Keywords: Amyloidosis
ATTR-CM
ATTR-PN
Transthyretin
Amyloid
TTR
Lead sponsor: Eidos Therapeutics, a BridgeBio company
Sponsor class: INDUSTRY
First posted: 2024-08-21
Enrollment: 582
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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 between 40 and 75 years inclusive.

Eligibility 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.

Primary outcomes:
measure: Time to development of ATTR (ATTR-CM or ATTR-PN, whichever occurs first; centrally adjudicated)
timeFrame: Since randomization up to approximately 7 years or until the study is declared over
Secondary outcomes:
measure: Time to development of ATTR-CM (centrally adjudicated)
timeFrame: Since randomization up to approximately 7 years or until the study is declared over
measure: Time to development of ATTR-PN (centrally adjudicated)
timeFrame: Since randomization up to approximately 7 years or until the study is declared over
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine - Section of Cardiology
state: Connecticut
city: Washington
country: United States
facility: MedStar Washington Hospital Center - MedStar Heart and Vascular Institute
state: District of Columbia
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Chicago
country: United States
facility: John H. Stroger, Jr. Hospital of Cook County
state: Illinois
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Kansas City
country: United States
facility: St. Luke's Hospital of Kansas City
state: Missouri
city: New Brunswick
country: United States
facility: Rutgers-Robert Wood Johnson Medical School
state: New Jersey
city: New York
country: United States
facility: New York University (NYU) School of Medicine - Langone Medical Center
state: New York
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC)
state: South Carolina
city: Greenville
country: United States
facility: Prisma Health Cancer Institute
state: South Carolina
city: Austin
country: United States
facility: National Neuromuscular Research Institute
state: Texas
city: Sofia
country: Bulgaria
facility: UMHAT Aleksandrovska Sofia, Clinic of Neurology Diseases
city: Le Kremlin-Bicetre
country: France
facility: AP-HP Hopital Bicetre
city: Florence
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi
city: Pisa
country: Italy
facility: Fondazione Toscana Gabriele Monasterio per la Ricerca Medica e di Sanità Pubblica - Ospedale San Cataldo
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Huelva
country: Spain
facility: Hospital Universitario Juan Ramon Jimenez
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro
Study officials:
References: