Skip to content
Clinical Trials – home

Rare diseases

Investigational molecules

Locations

Our offerNewsroom

Not recruitingRare disease

Study of Olezarsen (ISIS 678354) in Patients with Severe Hypertriglyceridemia: Testing Effects on Triglyceride Levels

Verified siteInvestigational
Clinical Trials Concierge

Prefer not to search? Our Concierge searches the trials for you.

What is this trial about?

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

This clinical trial focuses on patients with Severe Hypertriglyceridemia, a condition characterized by very high levels of triglycerides (fats) in the blood. The study will test a medication called ISIS 678354 (also known as olezarsen), which is an antisense oligonucleotide - a type of drug that can influence how genes work in the body.

The purpose of this research is to determine how well ISIS 678354 works compared to placebo in reducing triglyceride levels in the blood. During the study, participants will receive either ISIS 678354 or placebo as an injection under the skin (subcutaneous injection). The treatment will continue for approximately 12 months, with regular monitoring of blood triglyceride levels and other health parameters.

The medication will be given alongside standard lipid-lowering treatments that patients are already taking. Throughout the study, researchers will measure various factors related to blood fats, including substances called Apolipoprotein C-III and different types of cholesterol. They will also monitor patients for potential health complications and check the amount of fat in the liver.

The research process

The trial runs in 5 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Initial medical assessment

    Your fasting triglyceride levels will be checked to confirm they are at least 500 mg/dL

    Your current lipid-lowering medications will be reviewed - they should be stable for at least 4 weeks before starting

  2. Step 2

    Treatment assignment

    You will be randomly assigned to receive either olezarsen (ISIS 678354) or placebo

    Neither you nor your doctor will know which treatment you are receiving

  3. Step 3

    Treatment period - first 6 months

    You will receive subcutaneous injections (shots under the skin)

    Your triglyceride levels will be measured regularly

    Key measurements will be taken at weeks 25 and 27

  4. Step 4

    Treatment period - months 7-12

    Treatment continues with regular injections

    Additional measurements will include:

    - Triglyceride levels

    - Apolipoprotein C-III (a protein that affects fat processing)

    - Remnant cholesterol

    - Non-HDL cholesterol

    Your liver fat content will be measured

  5. Step 5

    Final assessment

    Final measurements will be taken at week 53

    Your overall response to treatment will be evaluated

    Your triglyceride levels will be compared to the starting values

Who can join the trial?

7 criteria

  • Must be 18 years of age or older
  • Must have high levels of triglycerides (fats in the blood) of at least 500 mg/dL when measured after fasting
  • Must be currently taking lipid-lowering medications (medicines that help reduce fats in the blood) according to standard medical guidelines
  • Must have been on a stable dose of lipid-lowering medications for at least 4 weeks before starting the screening process
  • Both men and women can participate in the study
  • Must be willing to continue taking current lipid-lowering medications throughout the study period
  • Must be able to provide fasting blood samples (not eating or drinking anything except water for several hours before blood tests)

Who cannot join the trial?

14 criteria

  • Age below 18 years or above 75 years
  • Pregnant or breastfeeding women
  • History of acute pancreatitis (inflammation of the pancreas) within the past 6 months
  • Current use of medications that can significantly affect triglyceride levels (blood fats)
  • Uncontrolled diabetes (blood sugar levels not well managed)
  • Severe kidney disease or requiring dialysis
  • Severe liver disease
  • History of heart attack or stroke within the past 6 months
  • Active cancer or cancer treatment within the past 5 years
  • Participation in another clinical trial within the past 30 days
  • Known allergies to the study medication or its components
  • Alcohol or substance abuse within the past year
  • Mental conditions that could interfere with study compliance
  • Unstable medical conditions that could affect study results
Clinical Trials Concierge

Prefer not to search? Our Concierge searches the trials for you.

Tell us about your condition – we search every trial in Europe and connect you with the right site.

We usually reply within a few days

Verified sites

All sites with verified contact details – recruitment status may not be available; ask directly

Trial locations

Where you can join this trial

Countries are shaded by recruitment status. Click a recruiting country to ask about joining there.

Not recruiting
Not finding your country?

Not sure what to do next?

Joining a clinical trial can seem overwhelming. We guide you step by step, so you know exactly what to expect and how we support you through the process.

See the full process and FAQ

Investigated drugs

Olezarsen (also known as ISIS 678354) is a medication being studied for treating severe hypertriglyceridemia, a condition where there are very high levels of triglycerides (fats) in the blood. This medication is given as an injection under the skin (subcutaneously) and works by helping to reduce triglyceride levels in the bloodstream. It represents a new approach to treating patients who have difficulty controlling their triglyceride levels with currently available treatments.

What is already known about the treatment

Olezarsen - A novel investigational medication administered through subcutaneous injection that is being studied in Phase 3 clinical trials for the treatment of severe hypertriglyceridemia (extremely high levels of triglycerides in the blood). The drug belongs to the class of antisense oligonucleotides, which work by targeting specific genetic material to reduce the production of proteins involved in triglyceride metabolism. Olezarsen represents a potential new therapeutic option for patients with severe hypertriglyceridemia who may not respond adequately to currently available treatments, with its mechanism focusing on modifying the underlying genetic factors contributing to the condition.

Investigated diseases

Severe Hypertriglyceridemia - A metabolic disorder characterized by abnormally high levels of triglycerides (fat molecules) in the blood, specifically above 500 mg/dL. The condition develops when the body produces too many triglycerides or cannot break them down effectively. Excess triglycerides can accumulate in various organs, particularly the liver and pancreas. The condition can be inherited genetically or develop due to other health conditions. People with this disorder often have difficulty processing fats from their diet, leading to their accumulation in the bloodstream.
Trial detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase IIITrial ID2024-510696-38-00Protocol codeISIS 678354-CS5Estimated enrolment619 patientsSponsorIonis Pharmaceuticals Inc.

sourced from the EU Clinical Trials Register and site verification

Want to learn more about this trial or check if you can participate?

Clinical Trials Concierge

Prefer not to search? Our Concierge searches the trials for you.

Tell us about your condition – we search every trial in Europe and connect you with the right site.