AMYLOID

Study Name: ION-682884-CS2 (Amyloid)

Study Objective: A Phase 3 Global, Double-Blind, Randomized, Placebo‑Controlled

Study to Evaluate the Efficacy and Safety of ION-682884 in Patients with Transthyretin‑Mediated Amyloid Cardiomyopathy (ATTR CM)

Key Inclusion Criteria:

• Medical history of HF secondary to hereditary or wild-type ATTR-CM with at least:

A) prior hospitalization for HF, which may include hospitalization for arrhythmia or pacemaker/ICD (implantable cardioverter defibrillator) placement, OR

B) symptoms and signs of volume overload or elevated intracardiac pressure that either requires or required treatment with diuretics for clinical stabilization

• End-diastolic interventricular septum thickness of > 12 mm on screening echocardiogram
• Screening NT-proBNP ≥ 600 pg/mL by central lab. 4. New York Heart Association (NYHA) class I-III
• 6MWT ≥ 150 meters

 Key Exclusion Criteria:

• Hospitalization or urgent visit to ER/ED for worsening of HF with discharge date within

4 weeks prior to or during Screening

• Uncontrolled hypertension SBP > 160 or  DBP > 100 mmHg
• Prior liver or heart transplant, and/or Left Ventricular Assist Device (LVAD) or anticipated  liver transplant or LVAD within 1 year after randomization
•  Active infection requiring systemic antiviral or antimicrobial therapy that will not be   

               completed prior to Study Day 1

• Known history of or positive test for human immunodeficiency virus (HIV)