ARO-APOC3 for Chylomicronemia Syndrome

(PALISADE Trial)

Recruiting at 62 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

75 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called plozasiran in adults with a rare genetic disorder that causes very high blood fat levels. The drug aims to lower these fat levels by reducing a specific protein in the blood.

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.

What data supports the effectiveness of the drug ARO-APOC3 for treating Chylomicronemia Syndrome?

Research shows that targeting APOC3, a protein that affects fat levels in the blood, can significantly reduce triglyceride levels in patients with familial chylomicronemia syndrome. In a study, an APOC3 inhibitor reduced triglyceride levels by 56 to 86%, suggesting that ARO-APOC3 might also be effective. ^{1 2 3 4 5}

Is ARO-APOC3 safe for humans?

The research on similar treatments like volanesorsen and ISIS 304801, which target APOC3, shows they can significantly reduce triglyceride levels in patients with familial chylomicronemia syndrome. However, the studies do not provide detailed safety data, so it's important to consult with a healthcare provider for more information on potential side effects and safety. ^{1 2 3 6 7}

How does the drug ARO-APOC3 differ from other treatments for chylomicronemia syndrome?

ARO-APOC3 is unique because it targets and reduces the levels of apolipoprotein C-III (APOC3), which is known to increase triglyceride levels through mechanisms not involving lipoprotein lipase (LPL). This approach is different from other treatments, as there are currently no effective therapies for chylomicronemia syndrome except for extreme dietary fat restriction. ^{1 2 3 5 8}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Targeting APOC3 in the familial chylomicronemia syndrome. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Missense mutation Leu72Pro located on the carboxyl terminal amphipathic helix of apolipoprotein C-II causes familial chylomicronemia syndrome. [2006]

3. United States pubmed.ncbi.nlm.nih.gov

Volanesorsen and Triglyceride Levels in Familial Chylomicronemia Syndrome. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Multiorgan system dysfunction in the chylomicronemia syndrome. [2014]

5. United States pubmed.ncbi.nlm.nih.gov

Dissection of Clinical and Gene Expression Signatures of Familial versus Multifactorial Chylomicronemia. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Why Is Apolipoprotein CIII Emerging as a Novel Therapeutic Target to Reduce the Burden of Cardiovascular Disease? [2018]

7. England pubmed.ncbi.nlm.nih.gov

The effect of volanesorsen treatment on the burden associated with familial chylomicronemia syndrome: the results of the ReFOCUS study. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Familial chylomicronemia caused by a novel type of mutation in the APOE-CI-CIV-CII gene cluster encompassing both the APOCII gene and the first APOCIV gene mutation: APOCII-CIV(Nijmegen). [2006]