ARO-APOC3 for Dyslipidemia

Not currently recruiting at 127 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests ARO-APOC3, a treatment for dyslipidemia, which involves abnormal levels of lipids, such as cholesterol and triglycerides, in the blood. The trial aims to determine the best dosing schedule to manage these lipid levels. Participants receive a subcutaneous injection of ARO-APOC3 every three months. Eligible participants should have completed a related 12-month study and still meet the study requirements. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that ARO-APOC3 has undergone safety testing in humans. In one study, no serious or severe side effects occurred, which may reassure those considering trial participation. However, one participant experienced a temporary increase in a liver enzyme called ALT, indicating that side effects can occur, though they are not severe.

In another study, 71 out of 88 participants reported some side effects, suggesting that while most experienced reactions, they were not necessarily serious. The treatment has been tested at various doses, allowing researchers to understand its effects at different levels.

Overall, these findings suggest that ARO-APOC3 is generally well-tolerated, but like any treatment, side effects can occur. Participants should consider this information when deciding to join a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike most treatments for dyslipidemia that rely on statins or lifestyle changes, ARO-APOC3 offers a novel approach by directly targeting and reducing the production of apolipoprotein C-III (apoC-III), a protein that plays a key role in regulating triglyceride levels in the blood. This mechanism of action is different because it potentially addresses the root cause of elevated triglycerides rather than just managing the symptoms. Additionally, ARO-APOC3 is administered via a convenient subcutaneous injection once every three months, which could improve patient adherence compared to daily oral medications. Researchers are excited about these features as they offer new hope for effectively managing dyslipidemia, particularly for patients who struggle with existing treatments.

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

Research has shown that ARO-APOC3, the treatment under study in this trial, effectively treats dyslipidemia, a condition characterized by abnormal blood fat levels. One study found that ARO-APOC3 significantly lowered triglyceride levels. Triglycerides, fats in the blood, can increase heart disease risk if too high. The treatment also reduced LDL-C, often called "bad cholesterol," by 33% and decreased HDL-C, known as "good cholesterol," by 27%. These changes in fat levels can help prevent heart disease and related problems. ARO-APOC3 works by targeting and reducing a protein called APOC3 in the liver, which helps control blood fat levels. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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]

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]

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. evidence.nejm.org evidence.nejm.org/doi/full/10.1056/EVIDoa2200325

RNA Interference Therapy Targeting Apolipoprotein C-III in ... Silencing APOC3 hepatic protein expression is expected to reduce levels of triglycerides, non–high-density lipoprotein (HDL) cholesterol, and ...

3. ahajournals.org ahajournals.org/doi/10.1161/ATVBAHA.122.317966

Broadening the Scope of Dyslipidemia Therapy by ... In the multiple ascending dose study, triglyceride levels fell 63%, LDL-C levels were reduced by 33%, HDL-C concentrations fell 27%, and APOB ...

4. arrowheadpharma.com arrowheadpharma.com/news-press/arrowhead-presents-new-clinical-data-on-aro-apoc3-at-aha-2021/

Arrowhead Presents New Clinical Data on ARO-APOC3 at ... Summary. In patients with FCS compared with non-FCS, ARO-APOC3 achieved similar levels of reduction of APOC3 and changes in key lipid parameters ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04998201

NCT04998201 | Study of ARO-APOC3 in Adults With Mixed ... Study Overview. Participants who have met all protocol eligibility criteria will be randomly assigned to treatment (ARO-APOC3 or placebo) in a double-blind ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10618314/

Updates in Small Interfering RNA for the Treatment of ... No serious or severe adverse events were reported. In the AROAPOC31001 study, one patient receiving ARO-APOC3 experienced moderate transient ALT ...

7. withpower.com withpower.com/trial/phase-2-dyslipidemias-5-2022-17844

ARO-APOC3 for Dyslipidemia · Info for Participants 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 ...