Plozasiran for High Triglycerides

(MUIR-3 Trial)

Not currently recruiting at 499 trial locations

Overseen By Dylan Steen, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Arrowhead Pharmaceuticals

Must be taking: Lipid-lowering medications

Must not be taking: Hepatocyte-targeted siRNA

Disqualifiers: Acute pancreatitis, BMI >45, 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

Compensation: Varies

Number of Visits: 4

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of plozasiran for people with high triglycerides, which are blood fats that can increase health risks. Participants will receive either a plozasiran injection or a placebo (inactive substance) every three months. Those diagnosed with high triglycerides and already on medication to lower them may be suitable candidates. The goal is to determine if plozasiran can manage triglyceride levels better than current treatments. As a Phase 3 trial, this is the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but you must be on standard lipid-lowering medications unless you are intolerant. It's best to discuss your specific medications with the trial team.

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

Previous studies have shown that participants tolerated plozasiran well. Research indicates that when administered to healthy individuals, plozasiran was generally as safe as a placebo, causing no more side effects than a dummy treatment. Some studies noted a change in cholesterol levels, but overall, the treatment was considered safe. Another study found that long-term use of plozasiran continued to lower triglyceride levels without major safety issues. These findings suggest that plozasiran is generally safe for individuals with high triglycerides. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for high triglycerides?

Most treatments for high triglycerides focus on lifestyle changes or medications like fibrates and omega-3 fatty acids that help lower these fat levels in the blood. But Plozasiran works differently, using RNA interference technology to specifically target and reduce the production of a protein that contributes to high triglyceride levels. This new mechanism of action is what sets Plozasiran apart from existing options. Researchers are excited because this approach has the potential to offer more precise and effective control of triglycerides with fewer side effects.

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

Studies have shown that plozasiran, which participants in this trial may receive, effectively lowers triglyceride levels, a type of fat in the blood. Research indicates that plozasiran can reduce these levels by up to 74% after 24 weeks. In other trials, plozasiran lowered triglycerides by an average of 60% compared to a placebo, a substance with no active ingredients. The treatment targets a protein called APOC3, which decreases the amount of triglycerides in the blood. Overall, these findings suggest that plozasiran could be a promising option for people with high triglyceride levels. ^{1 5 6 7 8}

Are You a Good Fit for This Trial?

Adults with high triglycerides who have a stable blood sugar level (HbA1c ≤8.5%), can maintain a low-fat diet, and have LDL cholesterol levels within specific limits. Participants must have documented hypertriglyceridemia with certain fasting triglyceride levels, be on standard lipid-lowering medications unless intolerant.

Inclusion Criteria

Fasting low density lipoprotein-cholesterol (LDL-C) ≤ 130 mg/dL (≤3.37 mmol/L) at screening

My medical records show I have high triglycerides between 150 and 499 mg/dL.

Willing to follow diet counseling and maintain a stable low-fat diet

Exclusion Criteria

I have not had acute pancreatitis in the last 4 weeks.

Body mass index >45 kg/m^2

I haven't used specific liver-targeting gene therapies for fats in the last year, except inclisiran.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 4 doses of plozasiran or placebo by subcutaneous injection once every 3 months

12 months

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Plozasiran

Trial Overview The trial is testing Plozasiran injections against a placebo in adults with hypertriglyceridemia to see if it's safe and effective. Participants will receive four doses over the course of a year, with each dose given every three months.

How Is the Trial Designed?

Group I: Plozasiran Injection Experimental Treatment 1 Intervention

4 doses of plozasiran by subcutaneous (sc) injection

Group II: Placebo Placebo Group 1 Intervention

calculated volume to match active treatment by sc injection

Who Is Running the Clinical Trial?

Arrowhead Pharmaceuticals

Lead Sponsor

Trials

45

Recruited

6,200+

Published Research Related to This Trial

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]

Apolipoprotein C-III (apoC-III) is linked to higher triglyceride levels and increased risk of coronary artery disease (CAD), making it a target for new therapies.

Current and developing treatments, including statins and an antisense oligonucleotide targeting APOC3, aim to lower apoC-III levels, which may reduce triglycerides and subsequently lower cardiovascular risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting ApoC-III to Reduce Coronary Disease Risk. Khetarpal, SA., Qamar, A., Millar, JS., et al.[2018]

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]

ISIS 304801 significantly reduced plasma APOC3 levels in a dose-dependent manner, achieving reductions of up to 79.6% in patients not on fibrates and 70.9% in those receiving fibrate therapy, indicating its efficacy in lowering triglyceride levels.

The treatment was well-tolerated with no safety concerns reported during the 13-week study involving 85 patients, suggesting that ISIS 304801 is a safe option for managing elevated triglyceride levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antisense Inhibition of Apolipoprotein C-III in Patients with Hypertriglyceridemia. Gaudet, D., Alexander, VJ., Baker, BF., et al.[2022]

A study involving 115 plasma samples from adolescents and adults identified 161 metabolites associated with a rare APOC3 variant, indicating that targeting apoC-III can significantly influence lipid metabolism.

The findings suggest that therapies like volanesorsen, which target apoC-III, may not only reduce harmful triacylglyceride levels but also promote a healthier lipid profile, potentially improving metabolic health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic characterisation of disturbances in the APOC3/triglyceride-rich lipoprotein pathway through sample-based recall by genotype. Corbin, LJ., Hughes, DA., Chetwynd, AJ., et al.[2022]

Hypertriglyceridemia is a significant risk factor for cardiovascular disease and acute pancreatitis, highlighting the need for effective treatments beyond existing options like fibrates and ω-3 fatty acids.

Novel therapies, including apolipoprotein C-III inhibitors and fibroblast growth factor 21 analogues, are currently in early clinical development to better manage very high triglyceride levels and reduce cardiovascular risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Investigational and Experimental Therapeutics for the Treatment of Hypertriglyceridemia. Parthymos, I., Kostapanos, MS., Liamis, G., et al.[2022]

Icosapent ethyl, a purified omega-3 fatty acid, has been approved in Germany to reduce cardiovascular events in patients with hypertriglyceridemia and established cardiovascular disease or diabetes, showing its efficacy in this high-risk group.

New drugs targeting proteins like ApoC-III and ANGPTL3 are in development, with promising genetic data supporting their potential effectiveness, but larger long-term studies are needed to confirm their roles in treating hypertriglyceridemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New therapeutic approaches for the treatment of hypertriglyceridemia. Gouni-Berthold, I., Schwarz, J.[2022]

ApoC-III has been linked to lower triglyceride levels and a reduced risk of cardiovascular disease, making it a promising target for new treatments for dyslipidemia and CVD.

Clinical trials using antisense oligonucleotides to inhibit apoC-III have shown encouraging results, suggesting that targeting this protein could effectively manage lipid levels and cardiovascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Why Is Apolipoprotein CIII Emerging as a Novel Therapeutic Target to Reduce the Burden of Cardiovascular Disease? Taskinen, MR., Borén, J.[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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2404143

Plozasiran, an RNA Interference Agent Targeting APOC3, ... In this trial involving participants with mixed hyperlipidemia, we found that plozasiran significantly lowered triglyceride levels as compared ...

2. acc.org acc.org/About-ACC/Press-Releases/2024/04/07/11/45/plozasiran-reduces-triglyceride-levels-by-74-at-24-weeks

Plozasiran Reduces Triglyceride Levels by 74% at 24 Weeks The investigational drug plozasiran reduced triglyceride levels by an average of 74% after 24 weeks of use without causing any significant safety concerns.

3. arrowheadpharma.com arrowheadpharma.com/news-press/arrowhead-pharmaceuticals-presents-new-data-at-aha24-from-palisade-phase-3-study-and-open-label-extension-from-muir-and-shasta-2-studies-of-plozasiran/

Arrowhead Pharmaceuticals Presents New Data at AHA24 ... The goal of treatment with plozasiran is to reduce the level of APOC3, thereby reducing triglycerides and restoring lipids to more normal levels ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38583092/

Plozasiran (ARO-APOC3) for Severe Hypertriglyceridemia In this randomized clinical trial of patients with sHTG, plozasiran decreased triglyceride levels, which fell below the 500 mg/dL threshold of acute ...

5. jacc.org jacc.org/doi/10.1016/j.jacc.2025.03.496

Effect of Targeting ApoC-III With Plozasiran on Lipoprotein ... In recent clinical trials, plozasiran reduced triglyceride levels, relative to placebo, by an average of 60% with 25- and 50-mg plozasiran dosed ...

6. ir.arrowheadpharma.com ir.arrowheadpharma.com/news-releases/news-release-details/arrowhead-pharmaceuticals-presents-new-data-aha24-palisade-phase

Press Release Details Title: Plozasiran and Triglyceride Levels in Hypertriglyceridemia: Long-Term Efficacy and Safety Data from Subjects in an Open-Label ...

7. ahajournals.org ahajournals.org/doi/10.1161/circ.150.suppl_1.4139852

Abstract 4139852: Plozasiran and Triglyceride Levels in ... Extended open-label treatment with plozasiran in subjects with moderate to severely elevated TGs continue to show reductions of TG levels and safety.

8. cardiab.biomedcentral.com cardiab.biomedcentral.com/articles/10.1186/s12933-025-02929-9

Safety, pharmacokinetics and pharmacodynamics of ... Single SC administration of plozasiran at 25 or 50 mg was well tolerated in healthy Chinese subjects; in addition, plozasiran demonstrated the ...