Unknown Heart, Stroke & Blood NIHR-supported project Brain & Nervous System

A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicentre Study to Evaluate the Efficacy and Safety of ALXN2220 in Adult Participants with Transthyretin Amyloid Cardiomyopathy (ATTR-CM)

Funder NIHR (part of DHSC)
Recipient organisation NIHR Royal Free Clinical Research Facility
NIHR support Recorded as supported by this research centre
Period Feb 2025 — Ongoing

In plain English

AI plain-English summary

A faulty protein is silently clogging the heart muscle of thousands of people, and this trial tests whether an antibody can scrub those deposits away. This matters because current treatments for transthyretin amyloid cardiomyopathy (ATTR-CM) only stop new amyloid from forming—they cannot remove the toxic protein already lodged in heart tissue. That existing damage continues to stiffen the heart and drive worsening heart failure, even when patients take stabilisers or gene silencers. No approved therapy tackles this root cause. The trial will enrol roughly 1,000 participants, randomly assigning them to receive either ALXN2220 or a placebo by intravenous drip every four weeks. Neither patient nor doctor will know who gets which. ALXN2220 is a monoclonal antibody designed to latch onto the misfolded, deposited form of TTR while leaving the normal transport protein untouched, triggering the immune system to clear the amyloid. The primary endpoint is whether this clearance improves survival and reduces cardiovascular events over about 2.5 years. If the drug works, it could become the first therapy to reverse—not just slow—the progression of this fatal heart condition, fundamentally changing how ATTR-CM is managed.

View original technical description
Amyloidosis is a rare, progressive, fatal disease caused by the deposition of misfolded "amyloid” protein in tissues and organs. This is a faulty form of transthyretin (TTR), which is normally used for transporting thyroid hormone and vitamin A in the blood. ATTR-CM is a type of amyloidosis where misfolded TTR is predominantly deposited in the heart, causing damage to the heart muscle. ATTR-CM is an increasingly recognized cause of heart failure with poor prognosis and limited therapeutic options. Current treatment approaches focus on eliminating or stabilising the production of the amyloid protein. There are no approved therapies that remove deposited amyloid protein from organs, which can continue to cause worsening heart failure despite treatment with TTR stabilizers or gene silencers. The purpose of this study is to evaluate the efficacy and safety of ALXN2220 in adult participants with ATTR-CM. ALXN2220 is a human anti-ATTR monoclonal antibody. ALXN2220 selectively binds misfolded, deposited ATTR, with no binding to the normal TTR transport protein. This leads to immune-mediated clearance of ATTR deposits from tissues/organs. By depleting TTR amyloid deposits in the heart, ALXN2220 is expected to halt or reverse disease progression in ATTR-CM. The primary purpose of this study is to measure if ALXN2220 improves mortality and cardiovascular morbidity in participants with ATTR-CM. Prior to enrolment, participants will be assessed to ensure they are safe to dose. Approximately 1000 participants are expected to be enrolled. Participants will have a 2:1 chance to receive ALXN2220 or placebo every 4 weeks via an intravenous (IV) drip. In this double-blind study, neither the study doctor nor participants know which treatment they receive and the treatments will be randomly assigned. The total duration of the study from the first day of screening to the last visit is approximately 2.5 years for the last participant to enter the study.

Researchers

Marianna Fontana (Principal Investigator)

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