A Study to Investigate LDL-cholesterol Lowering With Inclisiran Compared to Bempedoic Acid in Patients With Atherosclerotic Cardiovascular Disease.

Launched by NOVARTIS PHARMACEUTICALS · May 22, 2024

Keywords

ClinConnect Summary

This clinical trial is studying two medications, Inclisiran and bempedoic acid (BPA), to see which one is better at lowering LDL cholesterol (often called "bad" cholesterol) in patients who are at high risk for heart problems due to a condition known as atherosclerotic cardiovascular disease. The trial will involve about 400 adult participants who have high LDL cholesterol levels (70 mg/dL or higher) even though they are already taking strong cholesterol-lowering medications called statins. The goal is to find out if Inclisiran is more effective than BPA in helping these patients reduce their cholesterol levels.

To be eligible for this trial, participants need to meet certain criteria, such as having a specific LDL cholesterol level and being on a stable cholesterol-lowering treatment for at least four weeks. They must also be classified as very high or high risk for cardiovascular events, which can include having a history of heart attacks or strokes, diabetes, or other significant health risks. Participants can expect to receive either Inclisiran or BPA and will be monitored closely throughout the study to assess how well each treatment works. It's important to know that this trial is currently recruiting participants, and it aims to provide valuable information that could help improve treatment options for patients with high cholesterol and heart disease.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Fasting LDL-C ≥ 70 mg/dL at screening
• • 2. Participants must be on a stable (≥ 4 weeks) and well-tolerated lipid-lowering regimen (with or without Ezetimibe \[10mg\]) that must include a high-intensity statin therapy with either atorvastatin ≥40 mg QD or rosuvastatin ≥20 mg QD in a maximally tolerated or maximally approved dose at screening
• 3. Participants categorized as very high or high CV risk, as defined below:
• * Very high risk participants with at least one of the following:
• • Documented ASCVD: ACS: Unstable angina or myocardial infarction, Stable angina, Coronary revascularization, Unequivocally documented ASCVD upon prior imaging, Stroke and Transient Ischaemic Attack (TIA), Peripheral artery disease (PAD)
• • Diabetes mellitus (DM) with target organ damage (defined as microalbuminuria, retinopathy, or neuropathy), or at least ≥ 3 major risk factors, or early onset of Type 1 DM of long duration (\< 20 years)
• • A calculated SCORE2 ≥ 7.5 % for age \< 50 years; SCORE2 ≥ 10 % for age 50-69 years; SCORE2-OP ≥ 15 % for age ≥ 70 years to estimate 10-year risk of fatal and non-fatal CVD
• • Pre-existing diagnosis of heterozygous familial hyper-cholesterolemia (HeFH) with ASCVD or with another major risk factor OR
• * High risk participants with at least one of the following:
• • Markedly elevated single risk factors, in particular total cholesterol \> 310 mg/dL, LDL-C \> 190 mg/dL, or blood pressure ≥ 180/110 mmHg
• • Pre-existing diagnosis of HeFH without other major risk factors
• • DM without target organ damage (defined as microalbuminuria, retinopathy, or neuropathy), with DM duration ≥ 10 years or other additional risk factor
• • Moderate chronic kidney disease (eGFR 30-59 mL/min/1.73m2)
• • A calculated SCORE2 2.5 to \< 7.5 % for age \< 50 years; SCORE2 5 to \< 10 % for age 50-69 years; SCORE2-OP 7.5 to \< 15 % for age ≥ 70 years to estimate 10-year risk of fatal and non-fatal CVD as defined by the cardiovascular risk categories in the 2019 ESC/EAS guideline (Mach et al 2020), and updated SCORE2 and SCORE2-OP (Hageman et al 2021, de Vries et al 2021, Visseren et al 2021). Further details for documented ASCVD will be provided in the protocol.
• • 4. Fasting triglyceride \< 400 mg/dL at screening
• Exclusion Criteria:
• • 1. Acute coronary syndrome, ischemic stroke, peripheral arterial revascularization procedure or amputation due to atherosclerotic disease \< 4 months prior to screening visit or V1.
• • 2. Planned or expected cardiac, cerebrovascular or peripheral artery surgery or coronary re-vascularization within 6 months after screening visit.
• • 3. Heart failure NYHA class IV at screening or V1.
• • 4. Participants on more than one other lipid-lowering drug on top of statin at screening visit.
• • 5. Previous treatment with a mAb directed towards PCSK9 (e.g., evolocumab, alirocumab) or planned use after screening visit.
• • 6. Previous treatment prior to screening with BPA within 90 days
• • 7. Previous exposure to Inclisiran or any other non-mAb PCSK9-targeted therapy, either as an investigational or marketed drug.

Trial Officials