A Study of Inclisiran to Prevent Cardiovascular Events in High-risk Primary Prevention Patients.

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Randomized, Double-blind, Placebo-controlled Multicenter Study to Evaluate the Effect of Inclisiran on Preventing Major Adverse Cardiovascular Events in High-risk Primary Prevention Patients (VICTORION-1 PREVENT)

Conditions
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Primary Prevention of Atherosclerotic Cardiovascular Disease

Intervention / Treatment
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* Drug: Inclisiran sodium 300 mg (equivalent to 284 mg inclisiran) in 1.5 mL
* Drug: Placebo in 1.5ml


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. 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/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inclisiran sodium 300mg<br>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 | Drug: Inclisiran sodium 300 mg (equivalent to 284 mg inclisiran) in 1.5 mL<br>* Subcutaneous injection in pre-filled syringe.<br>* Other names: KJX839;|
| Placebo Comparator: Placebo<br>Matching placebo in 1.5ml pre-filled syringe. Randomized in a 1:1 ratio with Inclisiran. | Drug: Placebo in 1.5ml<br>* Matching placebo in 1.5ml solution for injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to the first occurrence of 4P-MACE | 4-Point-Major Adverse Cardiovascular Events (4P-MACE): composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, and urgent coronary revascularization. | Time to the first occurrence of 4P-MACE (up to approximately 75 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to the first occurrence of 3P-MACE | 3-Point-Major Adverse Cardiovascular Events (3P-MACE): composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal ischemic stroke) | Time to the first occurrence of 3P-MACE (up to approximately 75 months) | 
| Total number of first or repeated CV events (4P MACE) | Total 4P-MACE (composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, and urgent coronary revascularization) | up to 75 months | 
| Total number of first or repeated CV events (3P MACE) | Total 3P-MACE (composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal ischemic stroke) | up to 75 months | 
| Time to occurrence of Cardiovascular death | CV death is defined as death due to cardiovascular events. | Time to Cardiovascular death (up to 75 months) | 
| Time to occurrence of death due to any reason | All-cause mortality is death due to any reason. | Time to all-cause mortality (up to 75 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coronary Artery Disease (CAD), Non-Obstructive Coronary Artery Disease (NOCAD), Coronary Artery Calcium, Coronary artery stenosis, Coronary angiogram, Inclisiran, PCSK9, primary prevention, cardiovascular disease, MACE, myocardial infarction, stroke, LDL-C, hyperlipidemia, hypercholesterolemia, dyslipidemia, cholesterol