Olezarsen for Chylomicronemia Syndrome

Recruiting at 10 trial locations

Overseen By Ionis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Ionis Pharmaceuticals, Inc.

Must be taking: Volanesorsen

Must not be taking: Systemic corticosteroids, Anabolic steroids

Disqualifiers: Investigational drug, Plasma apheresis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: Unknown

Duration: 209 weeks

24 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing olezarsen, a medication for people with FCS who have already tried another treatment. It aims to see if olezarsen is safe and effective by lowering a protein that affects blood fat levels.

Will I have to stop taking my current medications?

You can continue taking certain medications like statins, omega-3 fatty acids, fibrates, antidiabetic medications, oral anticoagulants, tamoxifen, estrogens, or progestins, as long as the dosage stays the same. However, you cannot take systemic corticosteroids or anabolic steroids within 6 weeks before the study or during it, unless approved by the study's medical monitor.

What data supports the effectiveness of the drug Olezarsen for Chylomicronemia Syndrome?

Research on similar drugs like volanesorsen, which also targets apolipoprotein C-III (a protein that affects fat levels in the blood), shows that it can significantly lower triglyceride levels in patients with familial chylomicronemia syndrome, a condition similar to chylomicronemia syndrome. This suggests that Olezarsen, which works in a similar way, might also be effective in reducing triglyceride levels. ^{1 2 3 4 5}

What safety data exists for Olezarsen in humans?

Olezarsen, also known as volanesorsen, has been studied in clinical trials for conditions like hypertriglyceridemia and familial chylomicronemia syndrome. These studies have shown that it can significantly reduce triglyceride levels, but the safety profile is still being evaluated in ongoing trials. While the trials focus on effectiveness, they also monitor safety, suggesting that it is generally safe, but more data is needed for a complete understanding. ^{2 3 4 6 7}

How is the drug Olezarsen unique in treating chylomicronemia syndrome?

Olezarsen is unique because it targets and reduces apolipoprotein C-III (apoC-III) production, which helps lower triglyceride levels through both lipoprotein lipase (LPL)-dependent and independent pathways, offering a novel approach for a condition with no effective therapies other than extreme dietary fat restriction. ^{1 2 3 8 9}

Eligibility Criteria

This trial is for adults with Familial Chylomicronemia Syndrome (FCS) who have tried a drug called volanesorsen but stopped due to side effects. They can't be on systemic steroids or have had plasma apheresis recently, and should not switch their current medications like statins or omega-3s during the study.

Inclusion Criteria

I stopped taking Waylivra® due to side effects and it's approved in my country.

I have FCS and have been treated with or am currently on volanesorsen.

I am taking medications like statins, omega-3s, diabetes, blood thinners, or hormone therapy and can keep my doses constant.

Exclusion Criteria

I haven't taken any experimental drugs or used new medical devices in the last month.

I haven't taken steroids or had plasma apheresis in the last 6 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

8 weeks

Treatment

Participants receive olezarsen every 4 weeks by subcutaneous injection

209 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

13 weeks

Extension

Treatment period extended for an additional 52 weeks until drug availability or program discontinuation

52 weeks

Treatment Details

Interventions

• Olezarsen

Trial Overview The trial tests Olezarsen's safety and how it affects the body in FCS patients previously treated with volanesorsen. It looks at how the body processes Olezarsen and its impact on lipid levels in participants.

Participant Groups

Group I: Olezarsen Experimental Treatment 1 Intervention

Olezarsen will be administered once every 4 weeks by subcutaneous (SC) injection for up to 209 weeks.

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

Findings from Research

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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Volanesorsen and Triglyceride Levels in Familial Chylomicronemia Syndrome. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Targeting APOC3 in the familial chylomicronemia syndrome. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Apolipoprotein C-III reduction in subjects with moderate hypertriglyceridaemia and at high cardiovascular risk. [2022]

4. England pubmed.ncbi.nlm.nih.gov

The effect of volanesorsen treatment on the burden associated with familial chylomicronemia syndrome: the results of the ReFOCUS study. [2018]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Volanesorsen: A New Era in the Treatment of Severe Hypertriglyceridemia. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

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

7. United Arab Emirates pubmed.ncbi.nlm.nih.gov

APOC-III Antisense Oligonucleotides: A New Option for the Treatment of Hypertriglyceridemia. [2019]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Missense mutation Leu72Pro located on the carboxyl terminal amphipathic helix of apolipoprotein C-II causes familial chylomicronemia syndrome. [2006]

9. Netherlands pubmed.ncbi.nlm.nih.gov

A three month-old infant with severe hyperchylomicronemia: molecular diagnosis and extracorporeal treatment. [2015]