1. Academic Validation
  2. Study design and rationale for the Olpasiran trials of Cardiovascular Events And lipoproteiN(a) reduction-DOSE finding study (OCEAN(a)-DOSE)

Study design and rationale for the Olpasiran trials of Cardiovascular Events And lipoproteiN(a) reduction-DOSE finding study (OCEAN(a)-DOSE)

  • Am Heart J. 2022 Sep;251:61-69. doi: 10.1016/j.ahj.2022.05.004.
Michelle L O'Donoghue 1 J Antonio G López 2 Beat Knusel 2 Baris Gencer 3 Huei Wang 2 You Wu 2 Helina Kassahun 2 Marc S Sabatine 4
Affiliations

Affiliations

  • 1 TIMI Study Group, Brigham and Women's Hospital, Boston, MA. Electronic address: [email protected].
  • 2 Global Development, Amgen, Thousand Oaks, CA.
  • 3 Cardiology Division, Geneva University Hospitals, Geneva, Switzerland; Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland.
  • 4 TIMI Study Group, Brigham and Women's Hospital, Boston, MA.
Abstract

Background: Data support lipoprotein(a) (Lp[Lp(a)]) being a risk factor for atherosclerotic Cardiovascular Disease (ASCVD). Olpasiran is a small interfering RNA molecule that markedly reduces Lp(a) production in hepatocytes.

Study design: The Olpasiran trials of Cardiovascular Events And lipoproteiN(a) reduction-DOSE finding study is a multicenter, randomized, double-blind, placebo-controlled dose-finding study in 281 subjects with established ASCVD and Lp(a) > 150 nmol/L. Patients were randomly allocated to one of 4 active subcutaneous doses of olpasiran (10 mg q12 weeks, 75 mg q12 weeks, 225 mg q 12 weeks, or 225 mg q24 weeks) or matched placebo. The primary objective is to evaluate the effects of olpasiran dosed every 12 weeks compared with placebo on the percent change in Lp(a) from baseline at 36 weeks. Enrollment is now complete and follow-up is ongoing.

Conclusions: OCEAN(a)-DOSE trial is assessing the Lp(a)-lowering efficacy and safety of olpasiran. These data will be used to determine optimal dosing and design for a cardiovascular outcomes trial.

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