A Phase IIb, randomised, double-blind, placebo-controlled, multicentre study to evaluate the efficacy and safety of concomitant use of eplontersen and ALXN2220 compared with eplontersen and placebo in adult participants with transthyretin-mediated amyloid cardiomyopathy (ATTR-CM).
Transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) is a rare condition where abnormal proteins build up in the heart muscle. Over time, this makes the heart stiff and less able to pump blood properly, leading to shortness of breath and tiredness. This Phase II clinical trial tests a new treatment combination. All participants will take eplontersen, a medicine that helps stop the body from producing the faulty protein. Alongside this, half the participants will receive an experimental medicine called ALXN2220, designed to clear away protein that has already built up, while the other half receive a dummy drug (placebo). Doctors will measure how well patients can exercise on a stationary bike or treadmill, check blood markers of heart strain, and assess daily quality of life. The aim is to see if combining these medicines can improve heart function and help patients feel better in daily life.
At a glance
What is this study about?
The heart is a muscle that pumps blood around your body. In people with ATTR-CM, a normal blood protein called transthyretin becomes unstable, changes shape, and forms clumps in the heart tissue. These protein deposits make the heart stiff and thick. As a result, the heart cannot relax and fill with blood as well as it should, leading to symptoms like fatigue, swelling, and breathlessness.
Currently, newer treatments focus on stopping the liver from making the faulty protein. In this trial, all patients receive a medicine called eplontersen (brand name Wainzua), which works like a brake on protein production. Researchers are also testing an additional experimental medicine called ALXN2220. While eplontersen aims to stop new protein clumps from forming, ALXN2220 is designed to help the body clear away the clumps that are already stuck inside the heart muscle.
By comparing eplontersen plus ALXN2220 against eplontersen plus an inactive placebo, doctors want to see if tackling the disease from both sides leads to better results. They will track changes in exercise capacity using a special fitness test, look at heart scans, check blood markers that show heart strain, and ask patients how their symptoms affect everyday activities.
Because this is a Phase II study, it is an important step in working out whether this combined approach is safe and truly beneficial before it could potentially be considered for wider use across the NHS.
Key takeaways
- Tests a combination of two medicines to see if clearing existing protein and stopping new build-up works best.
- All participants receive the active treatment eplontersen, alongside either ALXN2220 or a placebo.
- Aimed at adults aged 18 and older diagnosed with ATTR-CM.
- Involves exercise fitness tests, blood tests, heart scans, and symptom surveys.
- Participation is entirely voluntary and will not affect your standard NHS care.
Who may be eligible?
This trial is open to adults aged 18 and older who have a confirmed diagnosis of transthyretin-mediated amyloid cardiomyopathy (ATTR-CM). Both men and women can take part, whether their condition is inherited through their family genes or developed naturally as they got older.
To join, participants need to be able to complete light exercise testing safely, such as pedalling on a stationary bicycle or walking on a treadmill. People who have severe medical conditions outside of their heart disease, such as advanced kidney failure or liver disease, may not be able to take part.
The trial team will carry out detailed checks, including reviewing your medical history, looking at heart scans, and doing blood tests, to make sure taking part is completely safe for you.
Could this study suit you?
Answer these quick questions to see if you may be eligible. This is a guide only — the research team makes the final call.
- I am aged 18 or older.
- I have been diagnosed with ATTR-CM (transthyretin-mediated amyloid cardiomyopathy).
- I am well enough to do a light exercise test on a bike or treadmill.
- I do not have severe, uncontrolled liver or kidney problems.
- I am willing to attend regular hospital appointments for check-ups and treatments.
What does participation involve?
If you take part, you will attend regular hospital appointments at a specialist clinic over several months. You will receive eplontersen, which is given as an injection just under the skin using a pre-filled pen. You will also receive either ALXN2220 or an inactive placebo, given by an injection or drip into a vein. Neither you nor your study doctor will know whether you are receiving ALXN2220 or the placebo.
During your visits, the medical team will carry out health checks. These include exercise fitness tests (where you pedal a bike while breathing into a mask), heart scans, blood tests, and health questionnaires about your daily symptoms. The study team will support and monitor your health closely throughout the trial.
Potential risks and benefits
Locations (5)
- —UnverifiedGermany
- —UnverifiedItaly
- —UnverifiedSpain
- —UnverifiedFrance
- —UnverifiedSweden
Common questions
Will I definitely receive the new medicine?
Everyone in the trial will receive the active medicine eplontersen. However, you will have an equal chance of receiving either the new medicine (ALXN2220) or a dummy treatment (placebo) alongside it.
What is the exercise test involved in this study?
It is a cardiopulmonary exercise test (CPET). You will pedal a stationary exercise bike or walk on a treadmill while wearing a mask that measures how much oxygen your body uses.
Will I have to pay for the treatments or tests?
No. All study medicines, clinic visits, and trial-related tests are provided free of charge, and travel expenses are often reimbursed.
Can I carry on taking my usual heart medications?
Most standard heart medicines can be continued, but the study team will review all your prescriptions to make sure they are safe to take alongside the trial medicines.
What happens if I decide to leave the trial early?
You are free to leave the trial at any point without giving a reason. Your standard NHS medical care will continue as normal.
How to find out more
Always speak to your GP or specialist before deciding to take part in a study.
Interested in taking part?
Discussion
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