MAGNITUDE: A Phase 3 Study of NTLA-2001 in Participants With Transthyretin Amyloidosis With Cardiomyopathy (ATTR-CM)

To evaluate the efficacy and safety of a single dose of NTLA-2001 compared to placebo in participants with ATTR-CM.

This is a multinational, multicenter, double-blind, placebo-controlled study in approximately 1200 participants, who will be randomized to receive a single infusion of either NTLA-2001 or placebo.

Inclusion Criteria: * Documented diagnosis of ATTR amyloidosis with cardiomyopathy * Medical history of heart failure (HF) * Symptoms of HF are optimally managed and clinically stable within 28 days prior to administration of study intervention * Screening NT-proBNP, a blood marker of HF severity, greater than or equal to 600 pg/mL and less than 10,000 pg/mL Exclusion Criteria: * New York Heart Association (NYHA) Class IV HF * Polyneuropathy Disability score of IV (confined to wheelchair or bed) * Has hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection * History of active malignancy within 3 years prior to screening * RNA silencer therapy (patisiran, inotersen and/or eplontersen) within 12 months prior to dosing. Any prior vutrisiran use is not allowed * Initiation of tafamidis or acoramidis within 56 days prior to study dosing * Estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73m\^2 * History of liver disease * Uncontrolled blood pressure * Unable or unwilling to take vitamin A supplementation for the duration of the study