Primary Prevention of Atherosclerotic Cardiovascular Disease
Conditions
Keywords
Inclisiran, PCSK9, primary prevention, cardiovascular disease, MACE, myocardial infarction, stroke, LDL-C, hyperlipidemia, hypercholesterolemia, dyslipidemia, cholesterol, Coronary Artery Disease (CAD), Non-Obstructive Coronary Artery Disease (NOCAD), Coronary Artery Calcium, Coronary artery stenosis, Coronary angiogram
Brief summary
CKJX839D12302 is a pivotal Phase III study designed to test the hypothesis that treatment with inclisiran sodium 300 milligram (mg) subcutaneous (s.c.) administered on Day 1, Day 90, and every 6 months thereafter in patients at high cardiovascular (CV) risk without a prior major atherosclerotic cardiovascular disease (ASCVD) event will significantly reduce the risk of 4-Point-Major Adverse Cardiovascular Events (4P-MACE) defined as a composite of CV death, non-fatal myocardial infarction (MI), non-fatal ischemic stroke, and urgent coronary revascularization, compared to placebo.
Detailed description
The purpose of this study is to evaluate inclisiran sodium 300 mg s.c. (equivalent to 284 mg inclisiran) compared to placebo on reducing the risk of 4P-MACE in adult patients at high risk for their first major adverse cardiovascular event. Randomized participants will receive study medication (inclisiran or placebo), administered s.c. on Day 1, Day 90, then every 6 months thereafter. This is an event-driven study. Therefore, the study will continue until the required number of clinical events have occurred across both treatment arms, and all participants have a minimum of 3 years of follow-up during the double-blind treatment period.
Interventions
Subcutaneous injection in pre-filled syringe.
DRUGPlacebo in 1.5ml
Matching placebo in 1.5ml solution for injection
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* At an increased risk for a first MACE (i.e., no prior major ASCVD event), defined as any one of the following: 1. Evidence of atherosclerotic coronary artery disease (CAD) on computer tomography (CT) or invasive coronary angiogram defined as a coronary artery stenosis ≥20% but \<50% in the left main coronary artery or stenosis ≥20% but \<70% in any other major epicardial coronary artery, or 2. Coronary artery calcium (CAC) score obtained by CT-scan ≥100 Agatston units, or 3. High 10-year ASCVD risk ≥20%, or 4. Intermediate 10-year ASCVD risk 7.5% - \<20% with at least 2 risk-enhancing factors. * LDL-C ≥70 mg/dL (≥1.81 mmol/L) but \<190 mg/dL (\<4.91 mmol/L) at the screening visit. If on a background lipid lowering therapy, the dose should be stable for at least 4 weeks prior to the screening visit and the participant should be willing to remain on this background therapy for the entire duration of the study.
Exclusion criteria
* History of major ASCVD event. * History of, or planned, ischemia-driven revascularization in a coronary or extracoronary arterial bed prior to randomization * Absence of coronary atherosclerosis on a CT angiogram or an invasive coronary angiogram in the 2 years prior to randomization * Coronary artery calcium (CAC) score of 0 obtained in the 2 years prior to randomization * Active liver disease or hepatic dysfunction * Previous, current, or planned treatment with a monoclonal antibody (mAb) directed toward proprotein convertase subtilisin/kexin type 9 (PCSK9) (e.g., evolocumab, alirocumab) * Pregnant or nursing (lactating) women * Women of childbearing potential unless they are using effective methods of contraception while taking study treatment which includes for 6 months after last study drug administration Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to the first occurrence of 4P-MACE | Time to the first occurrence of 4P-MACE (up to approximately 75 months) | 4-Point-Major Adverse Cardiovascular Events (4P-MACE): composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, and urgent coronary revascularization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to the first occurrence of 3P-MACE | Time to the first occurrence of 3P-MACE (up to approximately 75 months) | 3-Point-Major Adverse Cardiovascular Events (3P-MACE): composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal ischemic stroke) |
| Total number of first or repeated CV events (4P MACE) | up to 75 months | Total 4P-MACE (composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, and urgent coronary revascularization) |
| Total number of first or repeated CV events (3P MACE) | up to 75 months | Total 3P-MACE (composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal ischemic stroke) |
| Time to occurrence of Cardiovascular death | Time to Cardiovascular death (up to 75 months) | CV death is defined as death due to cardiovascular events. |
| Time to occurrence of death due to any reason | Time to all-cause mortality (up to 75 months) | All-cause mortality is death due to any reason. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Colombia, Croatia, Czechia, Denmark, Estonia, France, Greece, Hong Kong, Hungary, India, Israel, Italy, Latvia, Lithuania, Malaysia, Mexico, Netherlands, Philippines, Poland, Portugal, Puerto Rico, Romania, Singapore, Slovakia, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States, Vietnam
Contacts
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed