Effect of Olpasiran on Major Cardiovascular Events in Patients with Atherosclerotic Cardiovascular Disease and Elevated Lipoprotein(a): A Randomized, Placebo-Controlled Study

The primary objective is to compare the efficacy of olpasiran versus placebo in reducing the risk of coronary heart disease death, myocardial infarction, or urgent coronary revascularization in subjects with atherosclerotic cardiovascular disease and elevated lipoprotein(a). 5

Secondary objectives include:

• Comparison of risks for cardiovascular death, ischemic stroke, or myocardial infarction.
• Evaluation of the change from baseline in Lp(a) levels.
• Assessment of risks related to cardiovascular death, coronary revascularization, and all-cause mortality.
• Evaluation of safety and tolerability of subcutaneous administration. 4
• Assessment of pharmacokinetics. 6

This study involves a total of 3,148 patients. The study population consists of both male and female individuals. Eligible participants are between the ages of 18 and 85 years. The population is characterized by a history of atherosclerotic cardiovascular disease, specifically evidenced by myocardial infarction or coronary revascularization. Inclusion requires an elevated lipoprotein(a) level of ≥ 200 nmol/L during screening. Additionally, participants must have maintained stable and optimized lipid-lowering therapy for at least two weeks prior to screening.

This Phase 3, double-blind, randomized, placebo-controlled, multicenter study is designed to assess the impact of olpasiran compared to a placebo on major cardiovascular events. The study population consists of patients diagnosed with atherosclerotic cardiovascular disease and elevated lipoprotein(a). The primary endpoint is the time to the first occurrence of coronary heart disease death, myocardial infarction, or urgent coronary revascularization. Secondary endpoints include the time to cardiovascular death or ischemic stroke, the percent change in lipoprotein(a) from baseline to week 48, and the evaluation of treatment-emergent adverse events. The research methodology involves a screening visit to confirm eligibility based on age, stable lipid-lowering therapy, and laboratory-confirmed lipoprotein(a) levels of ≥ 200 nmol/L. Following screening, participants are randomized to receive either olpasiran or a placebo via subcutaneous injection. The study includes follow-up assessments to monitor clinical outcomes and serum concentrations of the investigational product.

The investigational medicinal product is olpasiran, provided as a solution for injection in pre-filled syringe. This substance is administered via subcutaneous route.

The control group receives a placebo for AMG 890.

The primary efficacy endpoint is the time to the first occurrence of coronary heart disease death, myocardial infarction, or urgent coronary revascularization.

Secondary efficacy parameters include:

• Time to cardiovascular death, myocardial infarction, or ischemic stroke, whichever occurs first.
• Time to cardiovascular death, myocardial infarction, urgent coronary revascularization, or ischemic stroke, whichever occurs first.
• Percent change from baseline to week 48 in lipoprotein (a).
• Time to myocardial infarction.
• Time to coronary heart disease death or myocardial infarction, whichever occurs first.
• Time to urgent coronary revascularization.
• Time to coronary revascularization.
• Time to coronary heart disease death.
• Time to cardiovascular death.
• Time to death by any cause.
• Time to ischemic stroke.