Study to Evaluate ARO-APOC3 in Adults With Severe Hypertriglyceridemia

(SHASTA-2 Trial)

Recruiting at 107 trial locations

Overseen By Medical Monitor

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Arrowhead Pharmaceuticals

Disqualifiers: Pancreatitis, Bariatric surgery, HIV, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 12 weeks

229 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment called ARO-APOC3 for people with very high levels of blood fats. The treatment involves two injections and works by reducing a protein that helps control these fats. The goal is to see if it is safe and effective.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the study team for guidance.

What data supports the effectiveness of the drug ARO-APOC3?

Research shows that inhibiting APOC3 can significantly lower triglyceride levels, which are fats in the blood linked to heart disease and pancreatitis. In one study, patients with very high triglyceride levels saw a reduction of 56 to 86% after treatment with an APOC3 inhibitor, suggesting that ARO-APOC3 might be effective in managing conditions related to high triglycerides. ^{1 2 3 4 5}

Is the treatment ARO-APOC3 generally safe for humans?

There is some evidence from clinical trials that targeting APOC3, like with the antisense oligonucleotide treatment, can be a promising approach for managing certain conditions related to high triglycerides, but specific safety data for ARO-APOC3 in humans is not detailed in the available research. ^{4 6 7 8 9}

Eligibility Criteria

Inclusion Criteria

You are open to receiving guidance on your diet from the study team based on the local standard of care.

You agree to sign a written consent form and follow the study's rules.

If you can get pregnant, you must have a negative pregnancy test, not be breastfeeding, and agree to use birth control.

Exclusion Criteria

Major surgery within 12 weeks of first dose

Planned coronary intervention (e.g., stent placement or heart bypass) or any non-cardiac major surgical procedure throughout the study

Uncontrolled hypertension

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 2 subcutaneous injections of ARO-APOC3 or placebo on Day 1 and Week 12

12 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• ARO-APOC3
• Placebo

Participant Groups

Group I: ARO-APOC3 50 mg, Day 1 and Week 12 Experimental Treatment 1 Intervention

2 doses of ARO-APOC3 by sc injection

Group II: ARO-APOC3 25 mg, Day 1 and Week 12 Experimental Treatment 1 Intervention

2 doses of ARO-APOC3 by sc injection

Group III: ARO-APOC3 10 mg, Day 1 and Week 12 Experimental Treatment 1 Intervention

2 doses of ARO-APOC3 by subcutaneous (sc) injection

Group IV: Placebo, Day 1 and Week 12 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+

Findings from Research

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]

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

Apolipoprotein CIII induces monocyte chemoattractant protein-1 and interleukin 6 expression via Toll-like receptor 2 pathway in mouse adipocytes. [2021]

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

Antisense Inhibition of Apolipoprotein C-III in Patients with Hypertriglyceridemia. [2022]

3. England pubmed.ncbi.nlm.nih.gov

The next generation of triglyceride-lowering drugs: will reducing apolipoprotein C-III or angiopoietin like protein 3 reduce cardiovascular disease? [2021]

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

Targeting APOC3 in the familial chylomicronemia syndrome. [2022]

5. England pubmed.ncbi.nlm.nih.gov

APOC3 induces endothelial dysfunction through TNF-α and JAM-1. [2018]

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

Downregulation of NK cell activities in Apolipoprotein C-III-induced hyperlipidemia resulting from lipid-induced metabolic reprogramming and crosstalk with lipid-laden dendritic cells. [2021]

8. England pubmed.ncbi.nlm.nih.gov

CRISPR/Cas9-mediated knockout of APOC3 stabilizes plasma lipids and inhibits atherosclerosis in rabbits. [2022]

9. Ireland pubmed.ncbi.nlm.nih.gov

Lack of evidence for a liver or intestinal miRNA regulation involved in the hypertriglyceridemic effect of APOC3 3'UTR variant SstI. [2018]