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Study on the Effectiveness and Safety of Eplontersen for Patients with Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR-CM)

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What is this trial about?

A plain-language summary of the goals, design and what participants do

This clinical trial is focused on studying a condition called Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR-CM). ATTR-CM is a heart disease where abnormal proteins build up in the heart, affecting its function. The study will test a treatment called ION-682884, also known as Eplontersen, which is a type of medication called an antisense oligonucleotide. This medication is designed to target and reduce the production of the abnormal protein causing the disease. Participants in the study will receive either the ION-682884 treatment or a placebo, which is an inactive substance that looks like the treatment but does not contain the active medication.

The purpose of the study is to evaluate the effect of ION-682884 on heart-related health outcomes in patients with ATTR-CM. Participants will receive regular injections under the skin and will be monitored over a period of time to assess the treatment's impact on their heart health. The study will compare the number of heart-related events, such as heart failure or heart attacks, between those receiving the treatment and those receiving the placebo. The study aims to determine if ION-682884 can improve the health and quality of life for people with ATTR-CM.

Throughout the study, participants will continue to receive their usual care for ATTR-CM. The study will involve regular visits to the clinic for health assessments and to receive the injections. The overall goal is to see if ION-682884 can reduce the risk of serious heart problems and improve the well-being of patients with this condition. Participants' health and safety will be closely monitored by the study team throughout the trial.

The research process

The trial runs in 6 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Joining the study

    Upon joining the study, participation is confirmed through a process that ensures eligibility based on specific criteria related to health and medical history.

    Participants must meet certain health conditions, such as having a confirmed diagnosis of transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) and a history of heart failure.

  2. Step 2

    Randomization

    Participants are randomly assigned to one of two groups: one receiving the active medication, ION-682884, and the other receiving a placebo.

    The study is double-blind, meaning neither the participants nor the researchers know who is receiving the active medication or the placebo.

  3. Step 3

    Medication administration

    The active medication, ION-682884, or the placebo is administered as a subcutaneous injection.

    The placebo consists of a sterile solution of sodium chloride and riboflavin in water for injection.

  4. Step 4

    Treatment duration

    The treatment continues over a period that extends until the estimated end date of the study, which is November 15, 2025.

    Participants are monitored regularly to assess the effects of the treatment on cardiovascular health and overall well-being.

  5. Step 5

    Evaluation of outcomes

    The primary goal is to evaluate the effect of ION-682884 on cardiovascular outcomes, including death and clinical events related to heart health.

    Secondary outcomes include changes in walking distance and quality of life scores, assessed at specific intervals during the study.

  6. Step 6

    Completion of the study

    At the end of the study, data from all participants are analyzed to determine the effectiveness and safety of ION-682884 compared to the placebo.

    The results contribute to understanding the potential benefits of the medication for patients with ATTR-CM.

Who can join the trial?

11 criteria

  • Females must not be pregnant or breastfeeding. They should be either surgically sterile, post-menopausal, or not engaging in sexual activity. If they are sexually active and can have children, they must agree to use one highly effective birth control method.
  • If taking medication for heart failure, the dosage should be stable for at least two weeks before joining the study.
  • Participants must agree to take vitamin A supplements as outlined in the study plan.
  • Males must be surgically sterile, not engaging in sexual activity, or if sexually active with a woman who can have children, they or their partner must use a highly effective birth control method.
  • Participants must agree to genetic testing for changes in the transthyretin (TTR) gene if it hasn't been done before.
  • Amyloid deposits must be confirmed in heart or other tissues using special staining or imaging tests, with specific results, and no abnormal light chains ratio.
  • The thickness of the heart's interventricular septum must be more than 12 mm on an echocardiogram during screening.
  • Participants must have a history of heart failure due to hereditary or wild-type ATTR-CM, with either a previous hospital stay for heart failure or related issues, or symptoms that require treatment with diuretics (except certain types) for stabilization.
  • The level of a specific heart-related protein, N-terminal prohormone of brain natriuretic peptide (NT-proBNP), must be at least 600 pg/mL, or 1200 pg/mL if the participant has atrial fibrillation, as measured by a central lab.
  • Participants must be classified as New York Heart Association (NYHA) class I-III, which indicates the severity of heart failure symptoms.
  • Participants must be able to walk at least 100 meters in a 6-minute walk test (6MWT).

Who cannot join the trial?

8 criteria

  • Patients who have a different heart condition that is not related to Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR-CM).
  • Patients who are not receiving the standard care available for their condition.
  • Patients who are not within the specified age range for the study.
  • Patients who are not able to follow the study procedures or attend the required visits.
  • Patients who have other serious health issues that might interfere with the study.
  • Patients who are pregnant or breastfeeding.
  • Patients who have participated in another clinical trial recently.
  • Patients who have allergies or reactions to the study medication or similar drugs.
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Investigated drugs

ION-682884 is a medication being studied for its potential to help patients with a condition called transthyretin-mediated amyloid cardiomyopathy (ATTR-CM). This condition affects the heart and can lead to heart failure. The medication is being tested to see if it can reduce the risk of cardiovascular death and other heart-related problems in patients who are already receiving standard treatments for their condition.

What is already known about the treatment

ION-682884 – This medication is administered orally and is currently being studied in a Phase 3 clinical trial for its effectiveness and safety in treating Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR-CM). It is not yet approved for general medical use, as it is still under investigation. The main therapeutic indication for ION-682884 is to reduce cardiovascular death and recurrent cardiovascular events in patients with ATTR-CM. At the molecular level, it works by targeting and reducing the production of transthyretin, a protein that can misfold and form amyloid deposits in the heart. It is classified pharmacologically as an antisense oligonucleotide.

Investigated diseases

Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR-CM) – This is a condition where abnormal protein deposits, known as amyloid, accumulate in the heart tissue. These deposits are made up of transthyretin, a protein that normally transports thyroid hormone and vitamin A in the blood. Over time, the buildup of amyloid can cause the heart walls to become stiff, leading to difficulties in the heart's ability to pump blood effectively. As the disease progresses, patients may experience symptoms such as fatigue, shortness of breath, and swelling in the legs. The condition can also lead to complications like heart failure and arrhythmias. ATTR-CM is considered a rare disease, affecting a small percentage of the population.
Trial detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase IIITrial ID2024-514434-20-00Protocol codeION-682884-CS2Estimated enrolment1 323 patientsSponsorIonis Pharmaceuticals Inc.

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