Plozasiran for Hypertriglyceridemia

(SHASTA-5 Trial)

Recruiting at 18 trial locations

Overseen By Medical Monitor

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: Recent ASCVD, Heart failure, 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

Compensation: Varies

Number of Visits: 8

Duration: 12 months

288 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called plozasiran for individuals with severe hypertriglyceridemia (very high triglyceride levels in the blood) who have recently experienced at least two episodes of acute pancreatitis (sudden inflammation of the pancreas). Participants will receive either the actual treatment or a placebo (a substance with no therapeutic effect) to compare outcomes. The study aims to determine if plozasiran is effective and safe in reducing high triglyceride levels and preventing pancreatitis. Individuals may qualify if they have very high triglycerides and have experienced acute pancreatitis twice, with one episode occurring in the past year. As a Phase 3 trial, this study represents 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 requires participants to stay on their current lipid and triglyceride-lowering medications unless they are intolerant or have had treatment failure. The protocol does not specify stopping other medications.

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

Research has shown that plozasiran is a promising treatment for lowering triglycerides without major safety concerns. One study found that plozasiran reduced triglyceride levels by 74% after 24 weeks and did not cause significant side effects. Other research demonstrated that a single dose of either 25 mg or 50 mg was well tolerated in healthy participants, as they did not experience serious problems after receiving the treatment. These findings suggest plozasiran is generally safe for humans, encouraging those considering joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Plozasiran is unique because it targets hypertriglyceridemia through a novel mechanism of action. Unlike standard treatments like fibrates and omega-3 fatty acids, which primarily work by modifying lipid metabolism, Plozasiran uses RNA interference to specifically reduce the production of Apolipoprotein C-III, a protein that plays a key role in triglyceride regulation. This targeted approach offers the potential for more effective and sustained triglyceride reduction with fewer side effects. Researchers are excited about Plozasiran because its quarterly subcutaneous injection could offer a more convenient and less frequent dosing schedule compared to daily oral medications.

What evidence suggests that plozasiran might be an effective treatment for severe hypertriglyceridemia?

Research has shown that plozasiran, which participants in this trial may receive, can effectively lower very high levels of triglycerides in people with severe hypertriglyceridemia. In one study, plozasiran reduced triglyceride levels by 74% after 24 weeks. Another study found that triglyceride levels dropped below 500 mg/dL, which is important for reducing the risk of acute pancreatitis, a painful and serious condition where the pancreas becomes inflamed. Importantly, these studies did not identify any major safety issues. Overall, plozasiran appears to be a promising option for managing severe hypertriglyceridemia. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

Adults with severe hypertriglyceridemia who've had at least two acute pancreatitis events, one in the last year. They must have high fasting triglyceride levels and low LDL cholesterol, follow a low-fat diet, and be on standard lipid-lowering meds. Pregnant or breastfeeding women are excluded.

Inclusion Criteria

I am willing to follow a low-fat diet plan.

I am a male or a female not pregnant, not breastfeeding, and not planning to become pregnant.

My LDL cholesterol level is 130 mg/dL or lower.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive plozasiran 25 mg or placebo by subcutaneous injection every three months

12 months

4 visits (in-person)

Open-label extension

Participants receive plozasiran 25 mg by subcutaneous injection every three 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's effectiveness and safety by comparing it to a placebo. Participants will receive either Plozasiran or placebo every three months while maintaining their diet and medications. After the blind phase, they'll enter an open-label extension for 12 months.

How Is the Trial Designed?

Group I: Plozasiran Injection Experimental Treatment 1 Intervention

Plozasiran by SC injection every 3 months (Q3M) through completion of the randomized period Plozasiran by SC injection Q3M through completion of the OLE period

Group II: Placebo Experimental Treatment 1 Intervention

calculated volume to match active treatment by SC injection (randomized period)

Who Is Running the Clinical Trial?

Arrowhead Pharmaceuticals

Lead Sponsor

Trials

45

Recruited

6,200+

Citations

1. 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 ...

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 ... In multiple clinical studies, investigational plozasiran has demonstrated reductions in triglycerides and multiple atherogenic lipoproteins in ...

4. 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.

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. 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 ...