Study of Inclisiran to Prevent Cardiovascular (CV) Events in Participants With Established Cardiovascular Disease

Study Overview
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Brief Summary
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Study CKJX839B12302 is a pivotal Phase III trial to evaluate the benefits of inclisiran on major adverse cardiovascular (MACE) events in participants with established cardiovascular disease (CVD).

Detailed Description
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Purpose of this study is to test the hypothesis that treatment with inclisiran sodium 300 mg s.c. administered on Day 1, Month 3 (Day 90), and every 6 months thereafter taken in addition to well-tolerated high-intensity statin therapy in participants with established ASCVD will significantly reduce the risk of 3-Point-Major Adverse Cardiovascular Events (3P-MACE) defined as a composite of CV death, non-fatal myocardial infarction (MI) and non-fatal ischemic stroke. This will be compared to placebo in adjunct to well-tolerated high-intensity statin therapy.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Multicenter Trial, Assessing the Impact of Inclisiran on Major Adverse Cardiovascular Events in Participants With Established Cardiovascular Disease (VICTORION-2 PREVENT)

Conditions
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Atherosclerotic Cardiovascular Disease

Intervention / Treatment
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* Drug: Inclisiran sodium 300 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fasting LDL-C ≥ 70 mg/dL at randomization visit Stable (greater than or equal to 4 weeks) and well-tolerated lipid-lowering regimen (including e.g. with or without Ezetimibe) that must include a high-intensity statin therapy with either atorvastatin greater than or equal to 40 mg QD or rosuvastatin greater than or equal to 20 mg QD Established CV disease defined as ANY of the following three conditions Spontaneous Myocardial infarction ≥ 4 weeks from screening visit History of ischemic stroke occurred ≥ 4 weeks prior to the Screening visit Symptomatic peripheral arterial disease (PAD) evidenced by either intermittent claudication with ankle brachial index (ABI) < 0.85, prior peripheral arterial revascularization procedure, or, amputation due to atherosclerotic disease. Exclusion Criteria: Acute coronary syndrome, stroke, peripheral arterial revascularization procedure or amputation due to atherosclerotic disease < 4 weeks before screening visit Treatment with PCSK9 inhibitors (e.g. evolocumab, alirocumab) within 90 days or planned use post first study visit Planned or expected cardiac, cerebrovascular or peripheral artery surgery or re-vascularization within the 6 months after the first study visit Heart failure NYHA class III or IV Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver Previous exposure to inclisiran or any other non-mAb PCSK9-targeted therapy, either as an investigational or marketed drug within 2 years Severe concomitant non-CV disease that is expected to reduce life expectancy to less than 5 years History of malignancy that required surgery radiation therapy and/or systemic therapy during the 3 years prior to the first study visit Pregnant or nursing (lactating) women Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 40 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: randomized, double-blind, parallel group, placebo-controlled, multi-center, event-driven study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inclisiran sodium<br>Subcutaneous injection | Drug: Inclisiran sodium 300 mg<br>* Subcutaneously injected on Day 1, Month 3 (Day 90) and every 6 months thereafter until EOS visit<br>|
| Placebo Comparator: Placebo<br>Subcutaneous injection | Drug: Placebo<br>* Subcutaneously injected on Day 1, Month 3 (Day 90) and every 6 months thereafter until EOS visit<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Occurrence of 3P-MACE (3-Point Major Adverse Cardiovascular Events) | 3P-MACE is a confirmed composite endpoint which includes cardiovascular death, non-fatal myocardial infarction and non-fatal ischemic stroke. | From randomization to total follow-up time (up to 72 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Occurrence of Cardiovascular (CV) Death | CV death is defined as death due to cardiovascular events | From randomization to total follow-up time (up to 72 months) | 
| Time to First Occurrence of 4P-MACE (4-Point Major Adverse Cardiovascular Events) | A composite 4P- MACE is defined as CV death, non-fatal MI, non-fatal ischemic stroke and urgent coronary revascularization. | From randomization to total follow-up time (up to 72 months) | 
| Time to first occurrence of Major Limb Adverse Events (MALE) | Major Limb Adverse Events including acute lower limb ischemia, lower limb amputation due to ischemia, or urgent lower limb revascularization for ischemia | From randomization to total follow-up time (up to 72 months) | 
| Time to occurrence of all-cause death | All-Cause death is defined as: all deaths from randomization until up to 72 months | From randomization to total follow-up time (up to 72 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atherosclerotic cardiovascular disease, Hypercholesterolemia, Dyslipidemia, high cholesterol, Hyperlipidemia, Inclisiran, siRNA, KJX839