Summary

The purpose of this study is to: * Evaluate the efficacy of nucresiran compared to placebo on reducing all-cause mortality and cardiovascular (CV) events * Evaluate the efficacy of nucresiran compared to placebo on additional assessments of CV events and/or death * Evaluate the efficacy of nucresiran compared to placebo on patient-reported health status and health-related quality of life

Age: 18 Years to 85 Years old

Gender: All

Start Date: 07/02/2025

Primary Completion Date (Estimated): 05/28/2030

Study Completion Date (Estimated): 11/30/2032

Accepts Healthy Volunteers: No

Trial Purpose and Description

Eligibility Criteria

Age: 18 Years to 85 Years old

Gender: All

Accepts Healthy Volunteers: No

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