Efficacy and Safety of Early In-Hospital Inclisiran Initiation in Patients with Acute Coronary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to demonstrate the superiority of inclisiran compared to a placebo in reducing low-density lipoprotein cholesterol (LDL-C) at Day 150, when initiated in the hospital setting prior to or at discharge for patients with acute coronary syndrome. This intervention is administered in combination with standard of care, which includes statin therapy and potentially other lipid-lowering treatments. Secondary objectives include:

• The proportion of participants achieving pre-specified LDL-C targets, including levels below 70 mg/dL, 55 mg/dL, and 100 mg/dL, or a reduction of at least 50% from baseline.
• The mean change from baseline in LDL-C, assessed both as an average over all post-baseline visits and by individual visit.
• The change in PCSK9 levels from baseline to Day 150.
• The change in plasma lipoproteins and triglycerides from baseline to Day 150.
• The evaluation of overall safety and tolerability of the investigational treatment.

This study involves 165 participants diagnosed with recent onset acute coronary syndrome, which includes both ST-elevation myocardial infarction and non-ST-elevation myocardial infarction. The study population consists of both male and female patients aged 18 years or older. Eligible individuals are those hospitalized for an ACS event receiving medical treatment or percutaneous coronary revascularization. Selection is based on specific low-density lipoprotein cholesterol levels at screening, with requirements varying depending on prior statin therapy. Specifically, participants must have an LDL-C level of ≥70 mg/dL if previously treated with high-intensity statins, ≥100 mg/dL if treated with low or moderate-intensity statins, or ≥125 mg/dL if not previously treated with statins or if they exhibit statin intolerance. A baseline fasting LDL-C of ≥70 mg/dL is required for randomization, which must occur within seven days of hospital admission and by the time of discharge.

This Phase 3, randomized, double-blind, placebo-controlled study evaluates the efficacy and safety of early hospital initiation of inclisiran in patients diagnosed with acute coronary syndrome. Participants receive either a 300 mg subcutaneous injection of inclisiran or a placebo in combination with standard of care, which includes statin therapy such as atorvastatin or rosuvastatin. The screening process includes assessment of LDL-C levels and clinical eligibility following hospitalization for a STEMI or NSTEMI event. Randomization occurs within seven days of hospital admission and before or at discharge. The primary objective is to demonstrate superiority in LDL-C reduction from baseline to Day 150. Secondary endpoints include changes in PCSK9, apoB, VLDL, triglycerides, and the occurrence of adverse events. The total trial duration for recruitment and completion is estimated to be one year.

The experimental treatment consists of inclisiran administered via subcutaneous injection at a dose of 300 mg.

A placebo is utilized as a comparator for the experimental medication.

Background therapy involves the administration of statin medications as part of the standard of care. This includes rosuvastatin at a dose of 40 mg via oral use or atorvastatin at a dose of 80 mg via oral use.

The primary efficacy endpoint is the percent change in low-density lipoprotein cholesterol (LDL-C) from baseline to Day 150. Secondary efficacy assessments include the proportion of participants achieving specific LDL-C thresholds at Day 150, specifically levels below 70 mg/dL, below 55 mg/dL, and below 100 mg/dL for the subset with baseline levels ≥100 mg/dL. Additionally, the proportion of participants achieving a reduction of at least 50% from baseline in LDL-C at Day 150 will be evaluated.

Further efficacy parameters involve the calculation of the percent change and absolute change from baseline to the mean LDL-C during the double-blind treatment period. Longitudinal assessments of LDL-C will be conducted at Day 30, Day 90, and Day 150 to determine percent and absolute changes. The study will also measure the percent and absolute changes in proprotein convertase subtilisin/kexin type 9 (PCSK9) from baseline at Days 30, 90, and 150. Other lipid parameters assessed at Day 150 include apolipoprotein B (apoB), very-low-density lipoprotein cholesterol (VLDL), non-high-density lipoprotein cholesterol (non-HDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol, and triglycerides.