What is the mechanism of action of this treatment?

Common treatments for hypertriglyceridemia include fibrates, omega-3 fatty acids, niacin, and statins. Fibrates activate peroxisome proliferator-activated receptors (PPARs) to increase the oxidation of fatty acids and reduce triglyceride levels. Omega-3 fatty acids reduce hepatic triglyceride synthesis. Niacin inhibits the release of free fatty acids from adipose tissue, decreasing hepatic triglyceride production. Statins primarily lower LDL cholesterol but also have modest triglyceride-lowering effects. Olezarsen, an antisense oligonucleotide, reduces the production of ApoC-III, a protein that inhibits lipoprotein lipase, thereby enhancing the breakdown of triglycerides. These mechanisms are crucial for hypertriglyceridemia patients as they help lower triglyceride levels, reducing the risk of pancreatitis and cardiovascular diseases.

What side effects are associated with this type of intervention?

Common treatments for hypertriglyceridemia include antisense oligonucleotides like mipomersen, which target ApoC-III. Known side effects of mipomersen include injection site reactions such as erythema, as well as potential flu-like symptoms, liver enzyme elevations, and increased risk of hepatic steatosis. Other treatments like fenofibrate and omega-3 fatty acids can cause gastrointestinal issues, liver enzyme abnormalities, and muscle pain. It is important to monitor these side effects and discuss them with a healthcare provider.

What prior FDA approvals exist?

The FDA has approved several treatments for hypertriglyceridemia, including fibrates (e.g., fenofibrate), omega-3 fatty acid formulations (e.g., icosapent ethyl), and niacin. These treatments primarily work by reducing triglyceride levels through different mechanisms. While antisense oligonucleotides like Olezarsen, which target ApoC-III to lower triglycerides, are still under investigation, mipomersen, another antisense oligonucleotide targeting apoB, has been studied for its lipid-lowering effects. More evidence is needed to confirm the efficacy and safety of these newer therapies in reducing cardiovascular risk.

What other types of research exist?

Promising novel alternatives to Olezarsen for hypertriglyceridemia include: 1) Evinacumab, a monoclonal antibody targeting ANGPTL3, which has shown significant triglyceride reduction in clinical trials. 2) Volanesorsen, another antisense oligonucleotide targeting ApoC-III, which has demonstrated efficacy in lowering triglycerides. 3) Pemafibrate, a selective PPARα modulator, which has been effective in reducing triglycerides and is being studied for broader cardiovascular benefits.

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Olezarsen for High Triglycerides

Phase 3

Recruiting

Research Sponsored by Ionis Pharmaceuticals, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Fasting TG ≥ 500 mg/dL (5.65 mmol/L) at Screening and Qualification

Patients must be on lipid-lowering therapy that should adhere to standard of care (SOC) per local guidelines. Lipid-lowering medications should be optimized and stabilized for at least 4 weeks prior to Screening to minimize changes in these medications during the study.

Must not have

Estimated GFR < 30 mL/min/1.73 m^2

Timeline

Screening 3 weeks

Treatment Varies

Follow Up month 6 and 12

Awards & highlights

Summary

This trial tests olezarsen, a new drug, to see if it can lower blood fat levels in people with high triglycerides. The goal is to help those who may not respond to usual treatments by reducing their blood fat and preventing health problems. Olezarsen is a new drug being tested to address the unmet need for effective triglyceride-lowering treatments, as current medications often fail to achieve normal triglyceride levels.

Who is the study for?

This trial is for people with severe hypertriglyceridemia, a condition with very high levels of triglycerides in the blood. Participants must be on stable lipid-lowering therapy according to local guidelines for at least 4 weeks before joining. They can't join if they have severely impaired kidney function, uncontrolled diabetes (HbA1c ≥ 9.5%), or significantly elevated liver enzymes.

What is being tested?

The study tests Olezarsen's effectiveness against a placebo in reducing fasting triglyceride levels from the start of the trial. Patients will randomly receive either Olezarsen or a placebo to compare changes in their triglyceride levels.

What are the potential side effects?

Possible side effects of Olezarsen may include reactions at the injection site, fatigue, headache, and potential impacts on liver function which will be closely monitored during the trial.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My fasting triglycerides are 500 mg/dL or higher.

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I have been on stable cholesterol-lowering medication for at least 4 weeks.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My kidney function is severely reduced.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ month 6 and 12

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~month 6 and 12

This trial's timeline: 3 weeks for screening, Varies for treatment, and month 6 and 12 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Percent Change from Baseline in Fasting TG at 6 Months (Average of Weeks 25 and 27) Compared to Placebo

Secondary study objectives

Adjudicated Acute Pancreatitis Event Rate During the Treatment Period Compared to Placebo

Adjudicated Acute Pancreatitis Event Rate During the Treatment Period Compared to Placebo, in Participants with ≥ 2 Events of Adjudicated Acute Pancreatitis in 5 Years Prior to Enrollment

Adjudicated Acute Pancreatitis Event Rate from Week 13 to Week 53 Compared to Placebo

+9 more

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: OlezarsenExperimental Treatment1 Intervention

Olezarsen will be administered once every 4 weeks by subcutaneous (SC) injection from Week 1 through Week 49.

Group II: PlaceboPlacebo Group1 Intervention

Olezarsen-matching placebo will be administered once every 4 weeks by SC injection from Week 1 through Week 49.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Olezarsen

2022

Completed Phase 3

~1810

0 / 3Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for hypertriglyceridemia include fibrates, omega-3 fatty acids, niacin, and statins. Fibrates activate peroxisome proliferator-activated receptors (PPARs) to increase the oxidation of fatty acids and reduce triglyceride levels. Omega-3 fatty acids reduce hepatic triglyceride synthesis. Niacin inhibits the release of free fatty acids from adipose tissue, decreasing hepatic triglyceride production. Statins primarily lower LDL cholesterol but also have modest triglyceride-lowering effects. Olezarsen, an antisense oligonucleotide, reduces the production of ApoC-III, a protein that inhibits lipoprotein lipase, thereby enhancing the breakdown of triglycerides. These mechanisms are crucial for hypertriglyceridemia patients as they help lower triglyceride levels, reducing the risk of pancreatitis and cardiovascular diseases.

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Who is running the clinical trial?

Ionis Pharmaceuticals, Inc.Lead Sponsor

148 Previous Clinical Trials

14,958 Total Patients Enrolled

10 Trials studying Hypertriglyceridemia

3,248 Patients Enrolled for Hypertriglyceridemia

Media Library

ISIS 678354 Clinical Trial Eligibility Overview. Trial Name: NCT05079919 — Phase 3

Hypertriglyceridemia Research Study Groups: Olezarsen, Placebo

Hypertriglyceridemia Clinical Trial 2023: ISIS 678354 Highlights & Side Effects. Trial Name: NCT05079919 — Phase 3

ISIS 678354 2023 Treatment Timeline for Medical Study. Trial Name: NCT05079919 — Phase 3

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