2024-511263-28-00已完成4 期
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
适应症
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 1,776
- 试验地点
- 114
- 主要终点
- Proportion of participants achieving individual LDL-C target (< 55 mg/dL or < 70 mg/dL) at day 90
研究概览
简要总结
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
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •Participants on more than one other lipid-lowering drug on top of statin at screening 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.
- •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.
- •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.
- •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
结局指标
主要结局
Proportion of participants achieving individual LDL-C target (< 55 mg/dL or < 70 mg/dL) at day 90
Proportion of participants achieving individual LDL-C target (< 55 mg/dL or < 70 mg/dL) at day 90
次要结局
- Relative change (percentage from baseline to mean LDL-C level) over the double-blind treatment period.
- Proportion of participants experiencing at least one muscle-related AE as defined in the Standardized MedDRA Queries (SMQ) rhabdomyolysis / myopathy from day 1 to day 360.
- Proportion of participants experiencing self-reported pain. Annualized number of days participants experiencing self-reported pain from baseline to day 360.
- Change from baseline in SF-BPI pain severity score to day 360. Change from baseline in SF-BPI pain interference score to day 360. Proportion of participants with clinically relevant change in SF-BPI pain severity score from baseline to day 360. Proportion of participants with clinically relevant change in SF-BPI pain interference score from baseline to day 360.
研究者
Novartis Pharma Arzneimittel GmbH
Scientific
Novartis Pharma AG
研究点 (114)
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