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Investigating Lepodisiran for Reducing Cardiovascular Events in Adults with Elevated Lipoprotein(a) and Atherosclerotic Cardiovascular Disease or at Risk for a First Cardiovascular Event

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What is this trial about?

A plain-language summary of the goals, design and what participants do

This clinical trial investigates the effect of lepodisiran (LY3819469) on reducing major adverse cardiovascular events in adults with elevated lipoprotein(a). Lipoprotein(a) is a type of cholesterol particle in the blood that, when elevated, increases the risk of heart and blood vessel problems. Atherosclerotic cardiovascular disease occurs when fatty deposits (plaques) build up in the arteries, which can lead to serious health problems like heart attacks and strokes.

The purpose of this study is to determine if lepodisiran is more effective than placebo in reducing cardiovascular events in people with high lipoprotein(a) levels. The study includes adults who either already have atherosclerotic cardiovascular disease or are at risk for having their first cardiovascular event. Cardiovascular events being monitored include death related to heart disease, myocardial infarction (heart attack), ischemic stroke (when blood flow to the brain is blocked), and urgent procedures to restore blood flow to the heart.

Participants in this study will be randomly assigned to receive either lepodisiran or placebo. The study will track how many participants experience cardiovascular events over time to determine if the medication is effective at reducing these outcomes compared to placebo.

The research process

The trial runs in 6 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Initial Screening

    You will undergo screening to confirm your eligibility. This includes confirming your lipoprotein(a) level is at least 175 nmol/L (nanomoles per liter) through a blood test.

    The screening will also verify that you either have established atherosclerotic cardiovascular disease (narrowing of arteries due to plaque buildup) or are at risk for a first cardiovascular event based on specific risk factors.

  2. Step 2

    Randomization

    You will be randomly assigned to receive either Lepodisiran (the study medication) or a placebo (inactive substance). Neither you nor your doctor will know which group you're in.

    The randomization process ensures that participants have an equal chance of being assigned to either treatment group.

  3. Step 3

    Treatment Administration

    You will receive injections of either Lepodisiran or placebo throughout the study period.

    The study medication (Lepodisiran) or placebo will be administered as a solution for injection, sometimes with 0.9% sodium chloride.

    Your healthcare provider will administer these injections according to a predetermined schedule that will be explained to you.

  4. Step 4

    Follow-up Visits

    You will attend regular follow-up visits at the study center for monitoring.

    During these visits, healthcare providers will perform assessments that may include physical examinations, blood tests, and questions about your health and any symptoms you may be experiencing.

    The study will monitor for cardiovascular events, including heart-related death, non-fatal heart attacks, non-fatal strokes, and urgent heart procedures.

  5. Step 5

    Study Duration

    The study is scheduled to run from March 2024 through December 2028, though your individual participation length may vary.

    You will continue receiving the study treatment and attending follow-up visits throughout your participation period.

  6. Step 6

    Study Completion

    At the end of your participation, you will have a final assessment visit.

    The main outcome being measured is the time until you experience any component of what researchers call MACE-4 (Major Adverse Cardiac Events), which includes cardiovascular death, non-fatal heart attack, non-fatal stroke, or urgent heart procedure.

Who can join the trial?

8 criteria

  • You must have high levels of Lipoprotein(a) [Lp(a)] of 175 nanomoles per liter (nmol/L) or higher, as measured by the laboratory.
  • You must meet one of the following requirements:
    • Be 18 years or older with established atherosclerotic cardiovascular disease (hardening of the arteries that can lead to heart problems) with a previous heart-related event or procedure at least 90 days before screening. This includes:
      • Coronary artery disease (blockages in the heart arteries)
      • Cerebral vascular disease (problems with blood vessels in the brain)
      • Peripheral arterial disease (narrowing of blood vessels outside the heart and brain)
      • OR be 55 years or older and at risk for a first cardiovascular event (meaning you haven't had a heart attack, stroke, or similar event before) with specific risk factors.
      • If you're 55 years or older without a previous cardiovascular event, you must have either:
        • Documented coronary artery disease, carotid stenosis (narrowing of neck arteries), or peripheral artery disease without having had an event or procedure
        • Familial hypercholesterolemia (an inherited condition causing high cholesterol)
        • Or a combination of three or more high-risk factors for cardiovascular disease

Who cannot join the trial?

12 criteria

  • Current heart attack or unstable chest pain (a medical emergency where the heart isn't getting enough blood)
  • History of stroke (brain injury caused by interrupted blood flow) within the past 3 months
  • Planned cardiac surgery (heart surgery) or coronary intervention (procedure to open blocked heart arteries)
  • Severe heart failure (when the heart cannot pump blood effectively)
  • Uncontrolled high blood pressure
  • Severe liver disease
  • Severe kidney disease or requiring dialysis
  • Other serious medical conditions that might interfere with study participation
  • Participating in another clinical trial at the same time
  • Pregnant or breastfeeding women
  • Known allergic reaction to the study medication or similar drugs
  • Unable to give informed consent or follow study procedures
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Investigated drugs

  • Lepodisiran

    is a medication being studied for its potential to reduce the risk of major cardiovascular events in people who have elevated levels of Lipoprotein(a), often abbreviated as Lp(a). This is a type of cholesterol that can increase the risk of heart and blood vessel problems. The medication aims to help people who already have cardiovascular disease or are at risk for developing it.

  • Placebo

    is an inactive substance that looks like the real medication but contains no active ingredients. In this study, it's being used as a comparison to see if lepodisiran is effective at reducing cardiovascular events.

What is already known about the treatment

Lepodisiran – An investigational medication administered through injection that targets and reduces elevated lipoprotein(a) [Lp(a)], a type of cholesterol linked to increased cardiovascular risk. It works at the molecular level by interfering with RNA to decrease the production of Lp(a) in the liver, thereby lowering blood levels of this harmful substance. Lepodisiran is currently being studied in clinical trials (like the ACCLAIM-Lp(a) trial) for its potential to reduce major adverse cardiovascular events in people with established atherosclerotic cardiovascular disease or those at risk for first cardiovascular events. This medication represents a novel approach to addressing cardiovascular risk in patients for whom traditional lipid-lowering therapies may not adequately address Lp(a)-related risk.

Investigated diseases

  • Atherosclerotic Cardiovascular Disease

    A condition characterized by the buildup of plaque inside the arteries, which can narrow and stiffen them over time. This plaque consists of fats, cholesterol, calcium, and other substances found in the blood. As atherosclerosis progresses, blood flow becomes restricted, potentially limiting oxygen and nutrients to vital organs. The disease develops gradually over many years, often without symptoms until arteries are significantly narrowed. Inflammation plays a key role in the development and progression of the condition.

  • Elevated Lipoprotein(a)

    A genetic condition characterized by high levels of lipoprotein(a), or Lp(a), a particle in the blood similar to LDL cholesterol but with an additional protein attached. Lp(a) levels are primarily determined by genetics and remain relatively stable throughout a person's life. This condition can accelerate the development of atherosclerosis and increase the risk of cardiovascular events. Lp(a) promotes inflammation, damages blood vessel walls, and enhances blood clotting processes.

Trial detailsLast updated 9 Oct 2026
Age18+ yearsPhasePhase IIITrial ID2023-509190-23-00Protocol codeJ3L-MC-EZEFEstimated enrolment15 291 patientsSponsorEli Lilly & Co.

sourced from the EU Clinical Trials Register and site verification

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