MAGNITUDE: A Phase 3, Multinational, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of NTLA-2001 in Participants with Transthyretin Amyloidosis with Cardiomyopathy (ATTR-CM)

To evaluate the efficacy of NTLA-2001, as measured by the composite risk of CV-related mortality and CV events (urgent HF visits and hospitalizations due to HF, arrhythmia, or stroke), compared to placebo.

Inova Fairfax Medical Center 
3300 Gallows Rd  
Falls Church, VA, 22042

• 18 to 90 years of age inclusive, at the time of signing the informed consent.
• Medical history of HF as defined by one of the following:

i.Hospitalization for HF within 12 months prior to administration of study intervention (not due to arrhythmia or a conduction system disturbance treated with a permanent pacemaker).

 OR

ii. Clinical evidence of HF within 12 months prior to administration of study intervention (with or without hospitalization) manifested by signs and symptoms of volume overload or elevated intracardiac pressures (eg, elevated jugular venous pressure, shortness of breath, signs of pulmonary congestion on chest radiograph or auscultation, or peripheral edema).

• Participants must be willing to abstain from alcohol consumption during Screening through 64 days after administration of study intervention.
• Able to complete a distance of ≥ 100 m on the 6MWT at Screening.

• Amyloidosis attributable to non-TTR protein (eg, amyloid light-chain amyloidosis) or has known primary amyloidosis or leptomeningeal amyloidosis.
• NYHA Class IV HF at Screening.
• HF that in the opinion of the Investigator is primarily on the basis of ischemic heart disease (eg, documented history of myocardial infarction), hypertension, or uncorrected valvular disease, or any etiology for HF not primarily due to ATTR-CM.
• Has a PND score of IV (confined to wheelchair or bed) at Screening.
• Known family or personal history of a severe or unmanaged thrombotic disorder.