ARO-APOC3 for Chylomicronemia Syndrome

(PALISADE Trial)

Not currently recruiting at 70 trial locations

Overseen By Steven Geller, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Arrowhead Pharmaceuticals

Must not be taking: HIV antiretrovirals, siRNA, antisense

Disqualifiers: Diabetes, Pancreatitis, Hypertension, HIV, 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: Unknown

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ARO-APOC3 to evaluate its effectiveness and safety for individuals with familial chylomicronemia syndrome (FCS), a rare condition that causes very high fat levels in the blood. Participants will receive either the treatment or a placebo (a substance with no active drug) for a short period, followed by the treatment for two years. Ideal candidates for this trial are those with FCS who have very high triglycerides (a type of fat in the blood) that do not respond to standard treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using certain liver-targeted treatments or HIV medications. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that ARO-APOC3 (plozasiran) is likely to be safe for humans?

Studies have shown that plozasiran, the treatment being tested, is generally well-tolerated. Research found that it significantly lowered triglycerides, which are fats in the blood. This is a positive sign for people with familial chylomicronemia syndrome. Patients taking plozasiran reported fewer cases of pancreatitis, a painful swelling of the pancreas, compared to those who did not.

In another study, patients did not experience severe side effects from plozasiran. These findings suggest that the treatment is safe for people with this condition. However, like any treatment, some mild side effects might occur. Always consult a healthcare provider for more personalized information. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for chylomicronemia syndrome?

Researchers are excited about ARO-APOC3 (plozasiran) because it targets chylomicronemia syndrome in a novel way. Unlike current treatments that often focus on dietary modifications and medications like fibrates, ARO-APOC3 uses RNA interference technology to reduce the production of apolipoprotein C-III, a protein involved in fat metabolism. This innovative mechanism could lead to more effective management of triglyceride levels. Additionally, ARO-APOC3 is administered via subcutaneous injection, which may offer a convenient alternative to oral medications.

What evidence suggests that ARO-APOC3 might be an effective treatment for chylomicronemia syndrome?

In this trial, participants will receive either plozasiran (ARO-APOC3) or a placebo. Research has shown that plozasiran may help treat familial chylomicronemia syndrome (FCS). Specifically, studies found that patients taking plozasiran experienced an 80% drop in triglyceride levels. Lower triglycerides are important because they reduce the risk of pancreatitis, a painful swelling of the pancreas. In fact, plozasiran lowered the risk of sudden pancreatitis by 83%. These findings suggest that plozasiran could greatly improve life for people with FCS. ^{2 4 6 7 8}

Are You a Good Fit for This Trial?

Adults with familial chylomicronemia syndrome (FCS) who are willing to follow dietary advice and have very high fasting triglyceride levels. They must use effective contraception, not be pregnant or breastfeeding, and cannot have had major surgery or uncontrolled conditions like hypertension recently.

Inclusion Criteria

I am using or willing to use effective birth control and will not donate sperm while on the study and for 24 weeks after.

My fasting triglycerides are very high despite taking standard treatments.

I have been diagnosed with Familial Chylomicronemia Syndrome (FCS).

Exclusion Criteria

I am currently on HIV medication.

I was diagnosed with diabetes recently or my HbA1c level is 9.0% or higher.

I have not had pancreatitis in the last 3 months.

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 administered subcutaneously

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants receive 8 doses of plozasiran over a 2-year period

2 years

What Are the Treatments Tested in This Trial?

Interventions

• ARO-APOC3
• Placebo

Trial Overview The trial is testing ARO-APOC3 against a placebo in adults with FCS. Participants will receive either the drug or placebo through subcutaneous injections over a period, followed by an open-label extension where all get ARO-APOC3.

How Is the Trial Designed?

Group I: ARO-APOC3 (plozasiran) Experimental Treatment 1 Intervention

4 doses of plozasiran by subcutaneous (sc) injection (randomized period) 8 doses of plozasiran by sc injection (open-label period)

Group II: Placebo Placebo Group 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+

Published Research Related to This Trial

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]

Citations

1. ir.arrowheadpharma.com ir.arrowheadpharma.com/static-files/85178334-9cf1-4b2d-902a-0b766eb133e0

Interim Analysis of Open Label Extension of †The extrapolated curve shows expected results if participants had continued receiving placebo in the OLE study. AP event probabilities for the.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39225259/

Plozasiran for Managing Persistent Chylomicronemia and ... Patients with persistent chylomicronemia who received plozasiran had significantly lower triglyceride levels and a lower incidence of pancreatitis than those ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05089084

Study of ARO-APOC3 (Plozasiran) in Adults With Familial ... The purpose of AROAPOC3-3001 is to evaluate the efficacy and safety of ARO-APOC3 plozasiran) in adult participants with familial chylomicronemia syndrome (FCS).

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1933287425001837

Plozasiran decreases the risk of acute pancreatitis and ... Genetic Disorders. Plozasiran decreases the risk of acute pancreatitis and may improve quality of life in familial chylomicronemia syndrome.

5. arrowheadpharma.com arrowheadpharma.com/news-press/arrowhead-pharmaceuticals-presents-new-pivotal-phase-3-data-at-esc-2024-from-palisade-study-of-plozasiran-in-patients-with-familial-chylomicronemia-syndrome/

Arrowhead Pharmaceuticals Presents New Pivotal Phase 3 ... Plozasiran reduced triglycerides by 80% from baseline and reduced the risk of developing acute pancreatitis by 83%.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11000138/

Plozasiran (ARO-APOC3) for Severe Hypertriglyceridemia This randomized clinical trial assesses the safety and effectiveness of plozasiran, an investigational APOC3-targeted drug, in the reduction of serum ...

7. nejm.org nejm.org/doi/abs/10.1056/NEJMoa2409368

Plozasiran for Managing Persistent Chylomicronemia and ... Patients with persistent chylomicronemia who received plozasiran had significantly lower triglyceride levels and a lower incidence of pancreatitis than those ...

8. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.124.072860

Temporal Effects of Plozasiran on Lipids and Lipoproteins ... The most severe sequela is acute pancreatitis (AP). The treatment of persistent chylomicronemia is generally refractory to guideline-recommended ...