Study to understand if inclisiran is better than a placebo at lowering LDL-cholesterol,is safe and can have an impact on patient quality of life, when given along with other lipid lowering medications.

Trial details

Who runs it

Novartis Pharma AG

Trial code

EU 2024-511263-28-00

Record updated

2025. április 2.

Original description

To demonstrate the superiority of inclisiran on top of ongoing individually optimized LLT compared to placebo on top of ongoing individually optimized LLT on reaching a participant's individual LDL-C target as measured by the proportion of participants achieving individual LDL-C target (< 55mg/dL or < 70 mg/dL) at day 90Read full original descriptionShow less

Efficacy, safety, tolerability and quality of life of ongoing individually optimized lipid-lowering therapy with or without inclisiran (KJX839) – a randomized, placebo-controlled, double-blind multicenter phase IV study in participants with hypercholesterolemia

To demonstrate the superiority of inclisiran on top of ongoing individually optimized LLT compared to placebo on top of ongoing individually optimized LLT on reaching a participant's individual LDL-C target as measured by the proportion of participants achieving individual LDL-C target (< 55mg/dL or < 70 mg/dL) at day 90

Inclusion: Male or female participants ≥18 years of age; Very high risk participants with at least one of the following: • Documented Atherosclerotic cardiovascular disease (ASCVD) i Acute coronary syndrome: Unstable angina or myocardial infarction. ii Stable angina. iii Coronary revascularization. iv Unequivocally documented ASCVD upon prior imaging. v Stroke and TIA. vi 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 cardiovascular disease (CVD). • Pre-existing diagnosis of heterozygous familial hypercholesterolemia (HeFH) with ASCVD or with another major risk factor. 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. • Diabetes Mellitus (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); LDL-C levels: • in participants with very high cardiovascular risk: serum LDL-C ≥55 mg/dL. • in participants with high cardiovascular risk: serum LDL-C ≥70 mg/dL; Participant on a stable dose of a statin for ≥ 30 days at screening; Participants on the individual MTD of statin for ≥ 30 days at baseline; Fasting triglyceride < 400 mg/dL at screening and baseline.

Exclusion: Participants on more than one other lipid-lowering drug on top of statin at screening visit; Previous (within 90 days of screening), current or planned treatment with a monoclonal antibody (mAb) directed towards PCSK9 (e.g. evolocumab, alirocumab) at screening or baseline visit; Previous exposure to inclisiran or any other non-mAb PCSK9 targeted therapy, either as an investigational or marketed drug within 2 years prior to screening or baseline visit; Previous, current or planned treatment with LDL-apheresis at screening or baseline visit; Acute coronary syndrome, ischemic stroke or TIA, coronary revascularization or peripheral arterial revascularization procedure or amputation due to atherosclerotic disease < 3 months prior to the screening or baseline visit; Heart failure New York Heart Association (NYHA) class IV at screening or baseline visit; Liver and CK: (a) Active liver disease defined as any current infectious, neoplastic, or metabolic pathology of the liver or (b) unexplained alanine aminotransferase (ALT), aspartate aminotransferase (AST) elevation >3x ULN, or total bilirubin elevation > 2x ULN (except for participants with Gilbert's syndrome), or (c) creatine kinase (CK) >5x ULN at screening or baseline visit; Participant with severe renal impairment defined by eGFR <30 mL/min/1.73m2 as calculated by the Modification in Diet in Renal Disease (MDRD) formula at screening or baseline visit; Pregnant or nursing (lactating) women at screening or baseline visit; Women of child-bearing potential, unless they are using highly effective methods of contraception during dosing of study treatment; Participants with a known intolerance to rosuvastatin at screening or baseline visit.

EU CTIS 2024-511263-28-00