Olezarsen for High Triglycerides

Recruiting at 237 trial locations

Overseen By Ionis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Ionis Pharmaceuticals, Inc.

Must be taking: Lipid-lowering therapy

Disqualifiers: High HbA1c, Liver enzymes, Low GFR, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 13

Duration: 53 weeks

446 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called olezarsen to determine if it can lower high triglycerides, which are fats in the blood. High triglycerides can lead to heart problems, so finding an effective treatment is important. Participants will receive either olezarsen or a placebo (a look-alike with no active drug) every four weeks for almost a year. This trial suits individuals diagnosed with high triglycerides (500 mg/dL or higher) who are already taking medications to lower their cholesterol. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the development of a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires that participants stay on their current lipid-lowering medications, which should be stable for at least 4 weeks before the study starts. This means you should not stop taking these medications.

Is there any evidence suggesting that olezarsen is likely to be safe for humans?

Research has shown that olezarsen is generally safe for people. Previous studies indicate that it is well-tolerated when used correctly. The FDA has approved olezarsen to treat familial chylomicronemia syndrome (FCS), where it helps lower triglyceride levels in adults. This approval reflects confidence in its safety for that condition.

For those considering joining a trial for olezarsen, this information can be reassuring. While any treatment can have side effects, existing research and its FDA approval for FCS support olezarsen's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Olezarsen is unique because it targets high triglycerides with a novel approach. Unlike most treatments that focus on lifestyle changes or medications like fibrates and omega-3 fatty acids, Olezarsen works by using antisense oligonucleotides to inhibit the production of apolipoprotein C-III, a protein that plays a key role in triglyceride metabolism. This targeted mechanism has the potential to significantly lower triglyceride levels more effectively and with fewer side effects. Researchers are excited about Olezarsen because it promises a new way to manage high triglycerides, which could lead to better outcomes for patients at risk of cardiovascular diseases.

What evidence suggests that olezarsen might be an effective treatment for high triglycerides?

Research has shown that olezarsen, which participants in this trial may receive, can significantly lower triglycerides—fats in the blood—in individuals with high levels. Studies have found up to a 72% reduction in these fats compared to a placebo, indicating the reduction is unlikely due to chance. Olezarsen is also associated with an 85% decrease in sudden pancreas inflammation, known as acute pancreatitis. This treatment targets a specific protein involved in fat breakdown, helping to lower triglyceride levels. Overall, evidence supports olezarsen’s effectiveness in managing high triglycerides. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for people with severe hypertriglyceridemia, having fasting triglycerides of 500 mg/dL or higher. Participants should be on a stable lipid-lowering therapy for at least 4 weeks and willing to follow diet and lifestyle advice. Those with certain liver, kidney, or blood sugar conditions are excluded.

Inclusion Criteria

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

Participants must be willing to comply with diet and lifestyle recommendations as able.

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

Exclusion Criteria

Total bilirubin > 1.5 ULN unless due to Gilbert's syndrome

My kidney function is severely reduced.

Alanine aminotransferase or aspartate aminotransferase > 3.0 × upper limit of normal

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 12 weeks

Treatment

Participants receive olezarsen or placebo administered subcutaneously once every 4 weeks

53 weeks

13 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

13 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

up to 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Olezarsen
• Placebo

Trial Overview The study tests the effectiveness of Olezarsen in reducing fasting triglyceride levels compared to a placebo. Participants will receive either Olezarsen or a placebo injection and their change in triglyceride levels from the start of the study will be measured.

How Is the Trial Designed?

Group I: Olezarsen Experimental Treatment 1 Intervention

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

Group II: Placebo Placebo Group 1 Intervention

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

Olezarsen is already approved in United States, European Union for the following indications:

Approved in United States as Tryngolza for:

• adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS)

Approved in European Union as Olezarsen for:

• treatment of familial chylomicronemia syndrome

Who Is Running the Clinical Trial?

Ionis Pharmaceuticals, Inc.

Lead Sponsor

Trials

151

Recruited

27,800+

Dr. Brett P. Monia

Ionis Pharmaceuticals, Inc.

Chief Executive Officer since 2020

PhD in Pharmacology from the University of Pennsylvania, BSc in Molecular Biology and Analytical Chemistry from Stockton State College

Dr. Eric Bastings

Ionis Pharmaceuticals, Inc.

Chief Medical Officer

MD

Published Research Related to This Trial

Diabetic dyslipidemia in type 2 diabetes is characterized by high triglycerides and low HDL cholesterol, with insulin resistance playing a key role in its development, particularly through the action of apolipoprotein CIII (ApoCIII).

Volanesorsen, a new drug that inhibits ApoCIII, has shown promise in improving lipid profiles in patients with diabetic dyslipidemia, suggesting it could be an effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contribution of ApoCIII to Diabetic Dyslipidemia and Treatment With Volanesorsen. Zhang, J., Rocha, NA., McCullough, PA.[2019]

Volanesorsen, an antisense oligonucleotide targeting APOC3 mRNA, has shown strong efficacy in significantly reducing both apoC-III production and triglyceride levels, which are crucial for managing severe hypertriglyceridemia.

Current phase 3 trials are evaluating the safety and effectiveness of volanesorsen, highlighting its potential as a new treatment option for patients at high risk of pancreatitis and cardiovascular disease due to elevated triglyceride levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

APOC-III Antisense Oligonucleotides: A New Option for the Treatment of Hypertriglyceridemia. Schmitz, J., Gouni-Berthold, I.[2019]

Volanesorsen, an antisense oligonucleotide targeting APOC3 mRNA, significantly reduces both apolipoprotein-CIII production and triglyceride levels, making it a promising treatment for severe hypertriglyceridemia.

Current phase 3 trials are evaluating the efficacy and safety of volanesorsen, which could provide a new option for patients at risk of pancreatitis and cardiovascular disease due to high triglyceride levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of antisense oligonucleotide therapy against apolipoprotein-CIII in hypertriglyceridemia. Gouni-Berthold, I.[2018]

AKCEA-APOCIII-LRx significantly reduces levels of apolipoprotein C-III and triglycerides in healthy volunteers, with reductions of up to 92% and 77% respectively after a single dose, indicating its potential efficacy in treating hypertriglyceridaemia.

The treatment was well tolerated with minimal side effects, showing no serious safety concerns, which suggests it could be a safe option for improving lipid profiles in patients at risk for coronary heart disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-acetyl galactosamine-conjugated antisense drug to APOC3 mRNA, triglycerides and atherogenic lipoprotein levels. Alexander, VJ., Xia, S., Hurh, E., et al.[2020]

Volanesorsen, an antisense oligonucleotide targeting APOC3 mRNA, significantly reduced hepatic fat fraction (HFF) in patients with severe hypertriglyceridemia, showing a reduction of -3.02% in the COMPASS trial and -8.34% in the BROADEN trial, indicating its efficacy in lowering liver fat.

The treatment demonstrated a strong inverse correlation between baseline HFF and changes in HFF in the volanesorsen groups, suggesting that patients with higher initial liver fat may benefit more from the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

APOC3 inhibition with volanesorsen reduces hepatic steatosis in patients with severe hypertriglyceridemia. Prohaska, TA., Alexander, VJ., Karwatowska-Prokopczuk, E., et al.[2023]

In a clinical trial involving 114 patients with high triglyceride levels, olezarsen significantly reduced triglyceride levels by up to 60% compared to a 6% increase in the placebo group, demonstrating its efficacy in lowering triglycerides in patients at high risk for cardiovascular disease.

Olezarsen also led to significant reductions in other harmful lipoproteins and showed a good safety profile, with no major adverse effects on liver or kidney function, and only mild injection site reactions reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apolipoprotein C-III reduction in subjects with moderate hypertriglyceridaemia and at high cardiovascular risk. Tardif, JC., Karwatowska-Prokopczuk, E., Amour, ES., et al.[2022]

Volanesorsen, an antisense drug targeting apoC3 mRNA, significantly reduced levels of apoC-III on various lipoproteins (apoB, Lp(a), and apoA-I) by over 80% compared to placebo in patients with hypertriglyceridemia, indicating its potential efficacy in lowering cardiovascular risk.

The study utilized novel high-throughput ELISAs to measure lipoprotein-associated apoC-III, providing a new method for assessing cardiovascular risk factors and demonstrating that volanesorsen may effectively reduce triglycerides and associated cardiovascular risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduction in lipoprotein-associated apoC-III levels following volanesorsen therapy: phase 2 randomized trial results. Yang, X., Lee, SR., Choi, YS., et al.[2021]

Citations

1. ir.ionis.com ir.ionis.com/news-releases/news-release-details/tryngolzatm-olezarsen-approved-us-first-ever-treatment-adults

TRYNGOLZA™ (olezarsen) approved in U.S. as first-ever ... TRYNGOLZA shown to significantly reduce triglycerides and substantially reduce acute pancreatitis events in adults with FCS ; a rare, ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05355402

NCT05355402 | A Study of Olezarsen (Formerly Known as ... The purpose of the study is to evaluate the effect of olezarsen on percent change in fasting triglyceride (TG) levels compared to placebo at Months 6 and 12.

3. ir.ionis.com ir.ionis.com/news-releases/news-release-details/olezarsen-significantly-reduces-triglycerides-and-acute

Olezarsen significantly reduces triglycerides and acute ... Up to 72% (p<0.0001) placebo-adjusted mean reduction in fasting triglycerides –. – 85% (p=0.0002) reduction in acute pancreatitis events, ...

4. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2025/218614Orig1s000IntegratedR.pdf

218614Orig1s000 INTEGRATED REVIEW - accessdata.fda.gov of olezarsen effectiveness to substantiate the results of CS3 and provided supportive safety data. ... 678354-CS8 based on the pre-clinical data.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40888739/

Targeting APOC3 with Olezarsen in Moderate ... The primary outcome was the least-squares mean percent change in triglyceride level from baseline to 6 months among the patients with moderate ...

6. clinicaltrials.eu clinicaltrials.eu/inn/isis-678354-sodium-salt/

Isis 678354 Sodium Salt - Clinicaltrials.eu These trials aim to evaluate the safety, efficacy, and tolerability of the drug when administered subcutaneously to patients with high triglyceride levels, ...