A Study of Inclisiran to Prevent Cardiovascular Events in High-risk Primary Prevention Patients.
- Conditions
- Primary Prevention of Atherosclerotic Cardiovascular Disease
- Interventions
- Drug: Placebo in 1.5ml
- Registration Number
- NCT05739383
- Lead Sponsor
- Novartis Pharmaceuticals
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 14012
-
At an increased risk for a first MACE (i.e., no prior major ASCVD event), defined as any one of the following:
- 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
- Coronary artery calcium (CAC) score obtained by CT-scan ≥100 Agatston units, or
- High 10-year ASCVD risk ≥20%, or
- 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.
- 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/exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo in 1.5ml Matching placebo in 1.5ml pre-filled syringe. Randomized in a 1:1 ratio with Inclisiran. Inclisiran sodium 300mg Inclisiran sodium 300 mg (equivalent to 284 mg inclisiran) in 1.5 mL Inclisiran sodium 300 mg in 1.5 mL solution for injection (subcutaneous) in pre-filled syringe. Randomized in a 1:1 ratio with matching placebo
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
Trial Locations
- Locations (242)
Central Alabama Research
🇺🇸Birmingham, Alabama, United States
Ascension St Vincents
🇺🇸Birmingham, Alabama, United States
Eastern Shore Research Institute
🇺🇸Fairhope, Alabama, United States
G and L Research LLC
🇺🇸Foley, Alabama, United States
Longwood Research
🇺🇸Huntsville, Alabama, United States
CB Flock Corporation
🇺🇸Mobile, Alabama, United States
Mobile Heart Specialists
🇺🇸Mobile, Alabama, United States
The Center for Clinical Trials
🇺🇸Saraland, Alabama, United States
Alaska Heart and Vascular
🇺🇸Anchorage, Alaska, United States
Synexus
🇺🇸Glendale, Arizona, United States
Scroll for more (232 remaining)Central Alabama Research🇺🇸Birmingham, Alabama, United States