A Phase 3, Randomized, Multicenter, Double-Blind, Placebo-Controlled Study of Acoramidis for Transthyretin Amyloidosis Prevention in the Young (ACT-EARLY Trial)

Plain English Summary

Acoramidis Transthyretin Amyloidosis Prevention Trial in the Young (ACT-EARLY) Study in Asymptomatic Carriers of a Pathogenic TTR Variant is a Phase 3 clinical trial sponsored by Eidos Therapeutics, a BridgeBio company studying Amyloidosis, Amyloid Cardiomyopathy, Transthyretin Amyloidosis, Cardiomyopathies, Heart Diseases, Polyneuropathies. This trial tests if acoramidis can prevent or delay the development of heart or nerve damage in young adults who carry a gene for transthyretin amyloidosis (ATTR) but have no symptoms. It is for individuals aged 18-75 who have a confirmed genetic marker for ATTR but have not yet developed symptoms of the disease. Participants will take either acoramidis or a placebo pill daily for up to 7 years, with regular check-ups. Currently, there are no approved treatments to prevent ATTR in asymptomatic carriers; this trial explores an early intervention strategy. The trial aims to enroll 582 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you are between 18 and 75 years old and have a confirmed genetic test showing you carry a gene variant known to cause ATTR. You cannot join if you already have symptoms of ATTR in your heart or nerves, or if you have certain other serious health conditions like major organ dysfunction or cancer. You must not have received other treatments that modify TTR. You must be able to undergo heart imaging tests. This trial is studying Amyloidosis, Amyloid Cardiomyopathy, Transthyretin Amyloidosis, Cardiomyopathies, Heart Diseases, Polyneuropathies, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures whether acoramidis can delay or prevent the onset of ATTR-related heart or nerve disease, meaning it could help people with a genetic predisposition live without developin The specific primary outcome measures are: 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). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial matters because it aims to prevent a serious, progressive disease like ATTR from developing in individuals at high genetic risk, filling a critical gap in early intervention. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Amyloidosis, Amyloid Cardiomyopathy, Transthyretin Amyloidosis, Cardiomyopathies, Heart Diseases, Polyneuropathies, where improved treatment options are needed.

Investor Insight

This trial targets a significant unmet need in a rare disease space, with a potential first-in-class preventative therapy for a genetically defined population, suggesting a strong market opportunity i Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 582 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor if you have a family history of ATTR or a positive genetic test for a TTR variant. Participation involves taking study medication daily and attending regular clinic visits for check-ups and tests over several years. You will be randomly assigned to receive either the study drug or a placebo, and neither you nor your doctor will know which you are receiving during the trial. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: QUADRUPLE
• Enrollment: 582 participants

Interventions

• DRUG: Acoramidis — TTR stabilizer administered orally twice daily (BID)
• DRUG: Placebo oral tablet — Non-active control administered orally twice daily (BID)

Primary Outcomes

• 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)

Secondary Outcomes

• Time to development of ATTR-CM (centrally adjudicated) (Since randomization up to approximately 7 years or until the study is declared over)
• Time to development of ATTR-PN (centrally adjudicated) (Since randomization up to approximately 7 years or until the study is declared over)

Full 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.

Trial Locations

• University of California, San Diego (UCSD) - Medical Center, La Jolla, California, United States
• University of California, Los Angeles (UCLA) - David Geffen School of Medicine, Los Angeles, California, United States
• University of California, San Francisco (UCSF), San Francisco, California, United States
• Stanford University, Stanford, California, United States
• University of Colorado Anschutz, Aurora, Colorado, United States
• Yale University School of Medicine - Section of Cardiology, New Haven, Connecticut, United States
• MedStar Washington Hospital Center - MedStar Heart and Vascular Institute, Washington D.C., District of Columbia, United States
• Mayo Clinic - Jacksonville, Jacksonville, Florida, United States
• Cleveland Clinic Florida, Weston, Florida, United States
• Emory University School of Medicine, Atlanta, Georgia, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Amyloidosis
• Transthyretin Amyloidosis
• Amyloid Cardiomyopathy
• Cardiomyopathies
• Heart Failure
• Hereditary Neuropathies
• Polyneuropathies
• Genetic Disorders
• Rare Diseases
• Preventative Medicine

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