Ocean(a)
Study Description
This study is being done to learn more about olpasiran (AMG 890) in people with cardiovascular disease and elevated Lp(a). It will see if olpasiran (AMG 890) reduces cardiovascular events, lowers Lp(a), and whether it causes any side effects.
Patients will be treated with the study drug olpasiran or placebo, randomly.
About 6,000 people are expected to take part in the study and are expected to be in the study for about 4.5 years.
Eligibility Summary
Inclusion Criteria:
1. Subject has provided informed consent prior to initiation of any study specificactivities/procedures.
2. Age 18 to 85 years (or legal age within the country if it is older than 18 years) at signing of informed consent.
3. Lp(a) > 200 nmol/L during screening by central laboratory.
At least 2 weeks of stable, and optimized lipid-lowering therapy consistent with regional/local clinical practice guidelines according to investigator’s judgment prior to screening Lp(a).
4. History of ASCVD as evidenced by history of either:
Myocardial infarction (presumed type 1 event due to plaque rupture/erosion)
and/or
Coronary revascularization by percutaneous coronary intervention (PCI) AND any of the following:
Age ≥ 65 years
Residual coronary artery stenosis > 50% in any major vessel (including major branches)
Multivessel PCI (ie, ≥ 2 distinct vessels including branch arteries)
Symptomatic peripheral arterial disease with either (a) intermittent claudication with ankle-brachial index (ABI) < 0.85, or (b) peripheral arterial revascularization or amputation due to atherosclerotic disease
Ischemic stroke (presumed atherosclerotic in origin)
Diabetes mellitus (type 1 or type 2).
Exclusion Criteria:
1. Severe renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 by central laboratory during screening.
2. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 x upper limit of normal (ULN), or total bilirubin (TBL) > 2 x ULN during screening.
3. History of hemorrhagic stroke.
4. History of major bleeding disorder (for example: hemophilia, von Willebrand disease, clotting factor deficiencies, etc).
5. Major cardiovascular event (eg, myocardial infarction, unstable angina, PCI, coronary artery bypass graft, or stroke) within 4 weeks prior to Lp(a) screening or during screening.
6. Planned cardiac surgery or arterial revascularization.
7. Malignancy (except non-melanoma skin cancers, cervical in-situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma) within the last 5 years prior to study day 1.
8. Diagnosis of severe heart failure (New York Heart Association Functional Classification IV, and/or if available, most recent left ventricular ejection fraction < 30%).
9. Uncontrolled or recurrent ventricular tachycardia in the past 3 months prior to study day 1.
10. Atrial fibrillation or flutter not on an anticoagulant despite an indication to be anticoagulated.
11. Uncontrolled hypertension at screening, defined as systolic blood pressure > 180 mmHg or diastolic blood pressure >110 mmHg at rest despite antihypertensive therapy.
12. Fasting triglycerides > 400 mg/dL (4.52 mmol/L) during screening.
13. Poorly controlled diabetes mellitus (type 1 or type 2), defined as HbA1c > 10% by central laboratory at screening.
14. Known major active infection, or a chronic disease or infection (eg, human immunodeficiency virus) that is not currently stable and appropriately managed in the judgment of the investigator.
15. Current or planned lipoprotein apheresis or < 3 months since last apheresis treatment prior to study day 1.
16. Subject has taken lomitapide in the last 12 months prior to study day 1.
17. Changes in lipid-lowering therapy after Lp(a) screening or within 4 weeks prior to day 1 (see Sections 6.1.6 and 6.7.2 for concomitant therapy requirements during study participation).
18. Previously received RNA therapy specifically targeting Lp(a), eg, olpasiran or pelacarsen.
19. Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded.
20. Female subjects of childbearing potential unwilling to use protocol specified method of contraception see Appendix 5 (Section 11.5) during treatment and for an additional 30 days after the last dose of investigational product.
21. Female subjects who are breastfeeding or who plan to breastfeed while on study through 30 days after the last dose of investigational product.
22. Female subjects planning to become pregnant while on study through 30 days after the last dose of investigational product.
23. Female subjects of childbearing potential with a positive pregnancy test assessed during screening by a highly sensitive urine or serum pregnancy test.
24. Subject has known hypersensitivity to olpasiran or any of the excipients.
25. Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, Clinical Outcome Assessments) to the best of the subject and investigator’s knowledge.
26. History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
Investigators
- Francesco Franchi, M.B.Ch.B. (M.D.)
Medicine