TRITON-CM: A Study to Evaluate Nucresiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy

Prior treatment

• Patients with current, prior or planning to receive TTR-lowering therapy, anti-TTR antibody treatment, diflunisal, or participating in another investigational study (must meet washout periods of previous treatment to be included).
• Patients with the following medical conditions: • significant non-TTR cardiomyopathies, unstable CHF, recent acute coronary syndrome, ventricular arrhythmias, pacemaker-indicated nodal dysfunction, or uncontrolled high blood pressure are excluded from the study. • untreated hypo- or hyperthyroidism • active infections requiring systemic antiviral, antiparasitic, or antimicrobial therapy that will not be completed before dosing • Prior or anticipated ( 12 months after randomization) organ transplant or implantation of LVAD • multiple drug allergies or history of allergic reaction to any component of study drug • intolerance to SC injection • other medical conditions or comorbidities that could interfere with study compliance or data interpretation, or a life expectancy of <2 years due to any non-cardiovascular condition

Other illness

• Unwilling or unable to limit alcohol consumption, with a history of alcohol use disorder within the last 12 months, or a history of illicit drug use within the past 5 years that could interfere with study compliance
• Has known HIV infection or evidence of current or chronic HCV or HBV infection.

Lab values

• NYHA Class IV HF; or NYHA Class III heart failure AND ATTR Amyloidosis Disease Stage 3 (defined as NT-proBNP >3000 ng/L and eGFR <45 mL/min)
• Has any of the following lab parameter at screening: a. AST or ALT levels ˃2.0×ULN; b. Total bilirubin >2.0×ULN; c. INR >1.5 (unless patients were on anticoagulant therapy in which case excluded if INR ˃3.5).
• Has an eGFR of <30 mL/min/1.73m2 at screening (calculation will be based on the CKD-EPI equation)

Other

• Has known primary amyloidosis (AL amyloidosis) or leptomeningeal amyloidosis
• Female patient is pregnant, planning a pregnancy, or breastfeeding
• Has a polyneuropathy disability Score IIIa, IIIb, or IV at the Screening visit.
• Unwilling to comply with the contraceptive requirements during the study;

• Age 18 (or age of legal consent per local regulations, whichever is older) to 85 years, inclusive.
• Documented diagnosis of ATTR amyloidosis with cardiomyopathy, classified as either hATTR amyloidosis with cardiomyopathy or wtATTR amyloidosis with cardiomyopathy:
• Medical history of HF with at least 1 prior hospitalization for HF OR clinical evidence of HF (with or without hospitalization)
• Patients may be receiving approved TTR stabilizers for ATTR amyloidosis. Patients may be receiving background therapy for HF but must be stable for at least 30 days prior to screening
• Patient is clinically stable, with no CV-related hospitalizations within 6 weeks prior to randomization
• Screening 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
• Patient is able to understand and is willing and able to comply with the study requirements and to provide written informed consent