Olezarsen for Chylomicronemia Syndrome

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of the drug olezarsen for people with chylomicronemia syndrome, a condition that causes fat buildup in the blood. The study focuses on individuals previously treated with the medication volanesorsen. Participants may continue using other medications for cholesterol, diabetes, or blood thinning if needed. This trial might suit someone diagnosed with chylomicronemia syndrome who has experienced issues with volanesorsen in the past. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment.

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.

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

Research has shown that olezarsen is a promising treatment for people with familial chylomicronemia syndrome (FCS). In one study, 66 patients with FCS received olezarsen, and the results were encouraging. The treatment significantly lowered triglyceride levels, which are fat particles in the blood. Importantly, patients tolerated the treatment well, with no major safety issues reported.

Additionally, olezarsen has already been approved in the U.S. and Europe to treat FCS. This approval indicates that the treatment is considered safe and effective for this condition. While every medication can have side effects, the existing approval and study results provide reassurance about its safety in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Chylomicronemia Syndrome, which often involve dietary restrictions and medications to lower triglyceride levels, Olezarsen offers a novel approach. Researchers are excited because Olezarsen works by targeting and reducing the production of apolipoprotein C-III, a protein that plays a key role in triglyceride metabolism. This unique mechanism has the potential to more effectively lower triglyceride levels compared to current options. Additionally, Olezarsen is administered via a convenient subcutaneous injection once every four weeks, offering a more manageable treatment regimen for patients.

What evidence suggests that olezarsen might be an effective treatment for chylomicronemia syndrome?

Research has shown that olezarsen, the treatment under study in this trial, can significantly lower triglyceride levels in people with familial chylomicronemia syndrome (FCS). Studies have found up to a 72% reduction in fasting triglycerides compared to a placebo. Additionally, there is an 85% decrease in sudden pancreas inflammation, known as acute pancreatitis, which is common in people with FCS. Several studies have tested the treatment, consistently showing positive results. Overall, olezarsen appears effective in reducing key symptoms of FCS. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

Citations

1. 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, ...

2. tryngolzahcp.com tryngolzahcp.com/about-tryngolza/trial-and-results

Clinical Trial Results & Efficacy The efficacy of TRYNGOLZA was evaluated in 45 adults with FCS. Participants were randomized to receive TRYNGOLZA or placebo once every 4 weeks for 6 months.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05130450

NCT05130450 | A Study of Olezarsen (Formerly Known as ... The purpose of this study is to evaluate the effect of olezarsen (formerly known as AKCEA-APOCIII-LRx) on the percent change in fasting triglycerides (TG) ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40231656/

Olezarsen for the Treatment of Familial Chylomicronemia ... Phase 2 and 3 trials showed consistent efficacy and safety profiles, with common adverse events including COVID-19 infection, abdominal pain, and diarrhea.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2666667724002228

279 a randomized, placebo-controlled phase 3 study of ... Olezarsen 80 mg significantly reduced TG levels and both olezarsen 50 and 80 mg groups demonstrated a marked reduction in AP events with a favorable safety and ...

6. 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, ...

7. ir.ionis.com ir.ionis.com/news-releases/news-release-details/tryngolzar-olezarsen-approved-european-union-familial

TRYNGOLZA® (olezarsen) approved in the European ... The approval is based on positive data from the Phase 3 Balance study, in which TRYNGOLZA 80 mg demonstrated a statistically significant ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/218614s000lbl.pdf

TRYNGOLZA (olezarsen) injection, for subcutaneous use The safety of TRYNGOLZA was evaluated in 66 patients with FCS enrolled in Trial 1 (NCT. #04568434) [see Clinical Studies (14)]. In this trial, 43 patients ...

9. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/34/NCT04568434/Prot_SAP_000.pdf

A Randomized, Double-Blind, Placebo-Controlled, Phase ... This study helped researchers find out if a drug called olezarsen could lower fat particles in blood (triglyceride levels) in participants who ...

10. ir.ionis.com ir.ionis.com/news-releases/news-release-details/ionis-announces-positive-olezarsen-topline-results-phase-3-study

Ionis announces positive olezarsen topline results from ... Olezarsen met the primary endpoint with a statistically significant reduction in triglyceride levels versus placebo; First study to show an ...