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

Novartis

Status and phase: Enrolling; Phase 3

Conditions: Primary Prevention of Atherosclerotic Cardiovascular Disease

Treatments: Drug: Inclisiran sodium 300 mg (equivalent to 284 mg inclisiran) in 1.5 mL; Drug: Placebo in 1.5ml

Study type: Interventional

Funder types: Industry

Identifiers

NCT05739383

CKJX839D12302

Details and patient eligibility

About

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.

Full 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.

Enrollment: 14,000 estimated patients

Sex: All

Ages: 40 to 79 years old

Volunteers: No Healthy Volunteers

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/exclusion criteria may apply.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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14,000 participants in 2 patient groups, including a placebo group

Inclisiran sodium 300mg

Experimental group

Description:

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

Treatment:

Drug: Inclisiran sodium 300 mg (equivalent to 284 mg inclisiran) in 1.5 mL

Placebo

Placebo Comparator group

Description:

Matching placebo in 1.5ml pre-filled syringe. Randomized in a 1:1 ratio with Inclisiran.

Treatment:

Drug: Placebo in 1.5ml