ARO-APOC3 for Dyslipidemia

Recruiting at 63 trial locations

Overseen By Medical Monitor

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Arrowhead Pharmaceuticals

Disqualifiers: Elevated HbA1c, AST, ALT, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

418 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that targeting apolipoprotein C-III (ApoC-III) can significantly lower triglyceride levels, which are fats in the blood linked to heart disease. Studies have found that reducing ApoC-III can decrease triglyceride levels by up to 86%, suggesting it could be an effective way to manage dyslipidemia and reduce cardiovascular disease risk. ^{1 2 3 4 5}

What safety data exists for ARO-APOC3 in humans?

The research does not provide specific safety data for ARO-APOC3 in humans, but it discusses the potential of targeting apolipoprotein C-III (apoC-III) to manage dyslipidemia and cardiovascular disease risk, suggesting that modulating apoC-III may be a promising therapeutic approach. ^{1 4 6 7 8}

How does the drug ARO-APOC3 work differently for dyslipidemia?

ARO-APOC3 is unique because it uses antisense technology to specifically target and inhibit the production of apolipoprotein C-III, a protein that plays a key role in triglyceride metabolism. This approach can effectively lower triglyceride levels and reduce the risk of cardiovascular disease, offering a novel mechanism compared to traditional treatments like statins or fibrates. ^{1 2 4 9 10}

What is the purpose of this trial?

This is an open-label extension of the parent studies AROAPOC3-2001 and AROAPOC3-2002. Adult participants with dyslipidemia who completed the blinded 12-month period from either parent study and continued to meet eligibility criteria had the option to be enrolled into this study. Eligible enrolled participants initially received open-label ARO-APOC3 every three or six months at the assigned dose level of the parent study until a final dose of 25 mg was selected, at which point all participants transitioned to the selected dosing regimen of 25 mg every 3 months.

Eligibility Criteria

This trial is for adults with dyslipidemia who completed a previous 12-month study (AROAPOC3-2001 or AROAPOC3-2002) and are not pregnant, nor planning to become pregnant. Participants must be willing to limit alcohol and have no new conditions that could affect their participation or increase risk.

Inclusion Criteria

I am not pregnant, not breastfeeding, and do not plan to become pregnant during the study.

Completed the 48-week study treatment period in the parent study

Able and willing to provide written informed consent

Exclusion Criteria

Any new condition or worsening of existing condition or any other situation that would make the subject unsuitable for enrollment, could interfere with the subject participating in or completing the study, would make it difficult to comply with protocol requirements or put the subject at additional safety risk

Unwilling to limit alcohol consumption to within moderate limits for the duration of the study

I was taken off ARO-APOC3 in a previous study due to high blood sugar or liver enzyme levels.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Open-label extension

Participants receive open-label ARO-APOC3 every three or six months at the assigned dose level until a final dose of 25 mg is selected, then transition to 25 mg every 3 months

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• ARO-APOC3

Trial Overview Participants will receive an open-label drug called ARO-APOC3. Initially, they'll get the dose from the prior studies until a final dose is chosen. Then everyone will switch to this selected dosing regimen to continue evaluating its effects on dyslipidemia.

Participant Groups

Group I: ARO-APOC3 Experimental Treatment 1 Intervention

1 dose of ARO-APOC3 by subcutaneous (sc) injection every 3 months

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]

AKCEA-APOCIII-LRx significantly reduces levels of apolipoprotein C-III and triglycerides in healthy volunteers, with reductions of up to 92% and 77% respectively after a single dose, indicating its potential efficacy in treating hypertriglyceridaemia.

The treatment was well tolerated with minimal side effects, showing no serious safety concerns, which suggests it could be a safe option for improving lipid profiles in patients at risk for coronary heart disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-acetyl galactosamine-conjugated antisense drug to APOC3 mRNA, triglycerides and atherogenic lipoprotein levels. Alexander, VJ., Xia, S., Hurh, E., et al.[2020]

References

1. 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]

2. 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]

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

Targeting APOC3 in the familial chylomicronemia syndrome. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Apolipoprotein C-III: understanding an emerging cardiovascular risk factor. [2022]

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

Inhibition of ApoCIII: the next PCSK9? [2022]

6. 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]

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

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

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

Lipid lowering activity of novel N-(benzoylphenyl)pyridine-3-carboxamide derivatives in Triton WR-1339-induced hyperlipidemic rats. [2018]

9. England pubmed.ncbi.nlm.nih.gov

N-acetyl galactosamine-conjugated antisense drug to APOC3 mRNA, triglycerides and atherogenic lipoprotein levels. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Apolipoprotein C-III: From Pathophysiology to Pharmacology. [2022]