Acoramidis Transthyretin Amyloidosis Prevention Trial in the Young (ACT-EARLY) Study in Asymptomatic Carriers of a Pathogenic TTR Variant
Purpose
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.
Conditions
- Amyloidosis
- Amyloid Cardiomyopathy
- Transthyretin Amyloidosis
- Cardiomyopathies
- Heart Diseases
- Polyneuropathies
Eligibility
- Eligible Ages
- Between 18 Years and 75 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
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.
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.
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Prevention
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental acoramidis |
Participants will receive acoramidis 712 mg orally BID (which is equivalent to 800 mg acoramidis HCl BID) |
|
|
Placebo Comparator Placebo |
Subjects will receive placebo to match twice daily |
|
Recruiting Locations
La Jolla 5363943, California 5332921 92037
Los Angeles 5368361, California 5332921 90095
San Francisco 5391959, California 5332921 94143
Stanford 5398563, California 5332921 94305
Aurora 5412347, Colorado 5417618 80045
New Haven 4839366, Connecticut 4831725 06519
Washington D.C. 4140963, District of Columbia 4138106 20010
Jacksonville 4160021, Florida 4155751 32224
Atlanta 4180439, Georgia 4197000 30322
Chicago 4887398, Illinois 4896861 60612
Chicago 4887398, Illinois 4896861 60637
Baltimore 4347778, Maryland 4361885 21201
Baltimore 4347778, Maryland 4361885 21287
Boston 4930956, Massachusetts 6254926 02114
Boston 4930956, Massachusetts 6254926 02115
Boston 4930956, Massachusetts 6254926 02118
Detroit 4990729, Michigan 5001836 48202
Rochester 5043473, Minnesota 5037779 55905
Kansas City 4393217, Missouri 4398678 64111
St Louis 4407066, Missouri 4398678 63110
New Brunswick 5101717, New Jersey 5101760 08901
New York 5128581, New York 5128638 10016
New York 5128581, New York 5128638 10029
New York 5128581, New York 5128638 10032
Rosedale 5134395, New York 5128638 11422
Durham 4464368, North Carolina 4482348 27710
Cleveland 5150529, Ohio 5165418 44195
Portland 5746545, Oregon 5744337 97239
Philadelphia 4560349, Pennsylvania 6254927 19104
Pittsburgh 5206379, Pennsylvania 6254927 15213
Charleston 4574324, South Carolina 4597040 29425
Greenville 4580543, South Carolina 4597040 89605
Austin 4671654, Texas 4736286 78759
Dallas 4684888, Texas 4736286 75390
Salt Lake City 5780993, Utah 5549030 84132
Falls Church 4758390, Virginia 6254928 22042
Richmond 4781708, Virginia 6254928 23219
More Details
- NCT ID
- NCT06563895
- Status
- Recruiting
- Sponsor
- Eidos Therapeutics, a BridgeBio company
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.