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Nucresiran for transthyretin amyloidosis with cardiomyopathy

TRITON-CM: A Phase 3 Global, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Nucresiran in Patients With Transthyretin-Mediated Amyloidosis With Cardiomyopathy (ATTR Amyloidosis With Cardiomyopathy)

Phase 3 Interventional Alnylam Pharmaceuticals · NCT07052903

This trial will test whether nucresiran can lower deaths and major heart-related events in people with transthyretin amyloidosis that affects the heart.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment1250 (estimated)
Ages18 Years to 85 Years
SexAll
SponsorAlnylam Pharmaceuticals Industry-sponsored
Locations207 sites (La Jolla, California and 206 other locations)
Trial IDNCT07052903 on ClinicalTrials.gov

What this trial studies

This Phase 3, randomized, placebo-controlled study compares nucresiran versus placebo (sterile saline) in adults with hereditary or wild-type ATTR cardiomyopathy. The primary focus is on reducing all-cause mortality and cardiovascular events, with additional measures including other CV outcomes and patient-reported health status and quality of life. Eligible patients have symptomatic heart failure (prior HF hospitalization or need for diuretics) and NT-proBNP within protocol-specified ranges; some background therapies such as TTR stabilizers are permitted. Key exclusions include very advanced heart failure (NYHA IV or NYHA III with stage 3 ATTR), advanced neuropathy, or severe renal impairment (eGFR <30). The sponsor is Alnylam Pharmaceuticals and sites are located in the United States.

Who should consider this trial

Good fit: Adults with hereditary or wild-type ATTR cardiomyopathy who have symptomatic heart failure (prior HF hospitalization or need for diuretics), meet the NT-proBNP and kidney function criteria, and are not NYHA class IV or severely neuropathic are the intended candidates.

Not a fit: Patients with very advanced heart failure (NYHA class IV or NYHA III plus stage 3 disease), advanced polyneuropathy, or severe renal impairment (eGFR <30) are unlikely to benefit and are excluded.

Why it matters

Potential benefit: If successful, nucresiran could reduce deaths and major cardiovascular events and improve quality of life for people with ATTR cardiomyopathy.

How similar studies have performed: Other TTR-lowering RNA therapies and the TTR stabilizer tafamidis have shown clinical benefit in ATTR, but randomized phase 3 evidence specifically for nucresiran in ATTR-CM is new.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria

* Has documented diagnosis of ATTR amyloidosis with cardiomyopathy including those with hereditary ATTR (hATTR) or wild-type ATTR (wATTR) amyloidosis.
* Has medical history of heart failure (HF) with at least 1 prior hospitalization for HF or signs and symptoms that require treatment with a diuretic.
* Has screening N-terminal prohormone B-type natriuretic peptide (NT-proBNP) \>300 ng/L and \<8500 ng/L; In patients with permanent or persistent atrial fibrillation, screening NT-proBNP \>600 ng/L and \<8500 ng/L.
* Patients may be receiving approved TTR stabilizers for ATTR amyloidosis (eg, tafamidis, acoramidis) and may be receiving background therapy for HF at the discretion of the Investigator.

Exclusion Criteria

* Has New York Heart Association (NYHA) Class IV HF; or NYHA Class III heart failure AND ATTR Amyloidosis Disease Stage 3.
* Has a polyneuropathy disability (PND) Score IIIa, IIIb, or IV.
* Has an estimated glomerular filtration rate eGFR of \<30 mL/min/1.73m\^2 at screening.
* Has received prior or currently receiving TTR-lowering therapy

Where this trial is running

La Jolla, California and 206 other locations

+157 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Transthyretin Amyloidosis With CardiomyopathyATTR-CMATTR amyloidosis with cardiomyopathyATTRHeriditary ATTRhATTRWild-type ATTRwATTR
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.