Study of ISIS 678354 (AKCEA-APOCIII-LRx) in Patients With Hypertriglyceridemia and Established Cardiovascular Disease (CVD)

Key Inclusion Criteria:

- Clinical diagnosis of CVD (defined as documented coronary artery disease, stroke, or
peripheral artery disease

- Fasting serum TG ≥ 200 mg/dL (≥ 2.3 mmol/L) and ≤ 500 mg/dL (≥ 5.7 mmol/L) at
Screening.

- Fasting TG ≥ 200 mg/dL and ≤ 500 mg/dL at Qualification visit.

- Must be on standard-of-care preventative therapy for known CVD risk factors

Key Exclusion Criteria:

- Within 6 months of Screening: acute coronary syndrome, major cardiac surgery, or
stroke/TIA

- Within 3 months of Screening: coronary, carotid, or peripheral arterial
revascularization, major non-cardiac surgery, or lipoprotein apheresis

- Heart failure New York Heart Association (NYHA) class IV

- Type 1 diabetes mellitus

- Type 2 diabetes mellitus with any of the following:

- Newly diagnosed within 12 weeks of screening

- HbA1c ≥ 9.0% at Screening

- Recent change in anti-diabetic pharmacotherapy (change in dosage or addition of
new medication within 12 weeks of screening [with the exception of ± 10 units of
insulin

- BMI > 40 kg/m2