Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS APO(a)-LRx in Healthy Volunteers With Elevated Lipoprotein(a)

A Blinded, Placebo-Controlled, Dose-Escalation, Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of ISIS 681257 Administered Subcutaneously to Healthy Volunteers With Elevated Lipoprotein(a)

The purpose is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of IONIS APO(a)-LRx (ISIS 681257) given to healthy volunteer subjects.

Inclusion Criteria:

• Must have given written informed consent and be able to comply with all study requirements
• Healthy males or females aged 18-65 inclusive and weighing ≥ 50 kg at the time of informed consent
• Females must be non-pregnant and non-lactating, and either surgically sterile or post- menopausal
• Males must be surgically sterile, abstinent or using an acceptable contraceptive method
• BMI < 35.0 kg/m2
• Subjects must have Lp(a) ≥ 75 nanomoles/liter nmol/L (30 mg/dL) at Screening

Exclusion Criteria:

• Known history of or positive test for human immunodeficiency virus (HIV), hepatitis C or chronic hepatitis B
• Treatment with another Study Drug, biological agent, or device within one-month of screening
• Regular use of alcohol within 6 months of Screening
• Use of concomitant drugs unless authorized by the Sponsor Medical Monitor
• Smoking > 10 cigarettes a day
• Considered unsuitable for inclusion by the Principal Investigator