Plozasiran for High Triglycerides

(SHASTA-10 Trial)

Recruiting at 21 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: Poor glycemic control, Acute pancreatitis, 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: 24 months

869 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 high triglycerides, which are fats in the blood that can cause health problems if elevated. The trial aims to assess how effectively plozasiran lowers triglycerides over time, particularly in those who have completed a previous related study. Participants should have a history of very high triglycerides and may have experienced issues like pancreatitis (inflammation of the pancreas). Those fitting this profile and involved in prior related studies may be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity 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. If you have diabetes, you must also be on an optimized antidiabetic regimen. There is no mention of stopping other medications, so you should discuss your specific situation with the study team.

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

Previous studies have shown that plozasiran lowers triglyceride levels by 74% over 24 weeks without major safety concerns, suggesting it is generally well-tolerated. Some research found that higher doses increased LDL cholesterol (a type of bad cholesterol), but these increases were not linked to serious side effects. Overall, existing data indicates the treatment appears safe. For those considering joining a clinical trial with plozasiran, this information may help in understanding the potential risks and benefits. ^{1 2 3 4 5}

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

Plozasiran is unique because it targets high triglycerides through a new mechanism of action. While most treatments for high triglycerides, like fibrates and omega-3 fatty acids, work by altering lipid metabolism, Plozasiran uses RNA interference to specifically reduce the production of apolipoprotein C-III, a protein that plays a key role in lipid regulation. This targeted approach could lead to more effective and precise treatment outcomes. Additionally, Plozasiran is administered via subcutaneous injection, which might offer a convenient alternative to daily oral medications. Researchers are excited about its potential to significantly lower triglyceride levels with this novel method.

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

Research has shown that plozasiran, the investigational treatment in this trial, can significantly lower triglyceride levels in individuals with very high blood fat levels. In one clinical trial, triglyceride levels dropped by an average of 74% after 24 weeks of treatment. Another study found reductions of up to 86% in triglycerides and 90% in APOC3, a protein related to fat processing. These findings suggest that plozasiran could effectively manage high triglyceride levels, often linked to pancreatitis and other health issues. The treatment has demonstrated these benefits without major safety concerns. ^{1 5 6 7 8}

Are You a Good Fit for This Trial?

Adults who've completed a prior study on hypertriglyceridemia can join this trial. They must consent to the study's procedures, agree to use effective contraception, and follow a low-fat diet. Pregnant or breastfeeding women are excluded.

Inclusion Criteria

I agree to use effective birth control during and after the study as required.

I am an adult, not pregnant, not breastfeeding, and willing to consent.

I completed all visits in my previous study (AROAPOC3-3001, 3003, 3004, or 3009).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive plozasiran administered subcutaneously every 3 months for 24 months

24 months

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue to receive plozasiran to evaluate long-term safety and efficacy

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Plozasiran

Trial Overview The trial is testing Plozasiran injections given every three months for two years in adults with high triglycerides. It aims to assess long-term safety and effectiveness while participants maintain a low-fat diet.

How Is the Trial Designed?

Group I: Plozasiran Injection Experimental Treatment 1 Intervention

8 doses of plozasiran (ARO-APOC3) administered by subcutaneous (SC) injection

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. 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 ...

3. 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.

4. ir.arrowheadpharma.com ir.arrowheadpharma.com/news-releases/news-release-details/arrowhead-pharmaceuticals-announces-new-phase-2-data-plozasiran

Press Release Details Plozasiran reduced triglycerides and APOC3 up to a mean maximum of 86% and 90% respectively in patients with severe hypertriglyceridemia.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06822790

Long-Term Safety and Efficacy of Plozasiran in Adults With ... This is an open-label study to be conducted in adults with hypertriglyceridemia (HTG) and severe hypertriglyceridemia (SHTG).

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 ... Here we report extension data to characterize long term safety and efficacy of plozasiran in subjects with elevated TGs. Plozasiran was studied ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06880770

NCT06880770 | Study of Plozasiran in Adults With Severe ... This study will evaluate the efficacy and safety of plozasiran in approximately 140 adult participants with severe hypertriglyceridemia (SHTG) and history of ...