ARO-APOC3 for Hypertriglyceridemia

(SHASTA-2 Trial)

No longer recruiting at 188 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a new treatment, ARO-APOC3, for individuals with severe hypertriglyceridemia, a condition characterized by very high triglyceride levels in the blood. Participants will receive two injections of ARO-APOC3 at varying doses or a placebo to determine if it safely lowers triglyceride levels. Suitable candidates have triglyceride levels exceeding 500 mg/dL and experience related health issues. As a Phase 2 trial, the research focuses on assessing the treatment's efficacy in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ARO-APOC3 has generally been well-tolerated in past studies. Participants did not experience more frequent or severe side effects with higher doses. Common side effects included muscle pain, dizziness, and tingling skin, affecting fewer than 10% of participants. Although serious issues like chest pain and gallstones occurred, they were mild to moderate and not directly linked to the treatment. Overall, ARO-APOC3 appears safe, with side effects similar to those of a placebo. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike traditional treatments for severe hypertriglyceridemia, which often include lifestyle changes and medications like fibrates or omega-3 fatty acids, ARO-APOC3 targets the problem at its genetic source. This treatment works by reducing the production of apolipoprotein C-III, a protein that plays a key role in regulating triglyceride levels in the blood. Researchers are excited because ARO-APOC3 is administered through a subcutaneous injection and has the potential to lower triglyceride levels more effectively and with fewer side effects than current options. With its novel approach, ARO-APOC3 could offer a new hope for patients who struggle to manage their condition with existing therapies.

What evidence suggests that this trial's treatments could be effective for severe hypertriglyceridemia?

Research has shown that ARO-APOC3, which participants in this trial may receive, can significantly lower triglyceride levels in individuals with severe hypertriglyceridemia, a condition characterized by very high levels of fat in the blood. In clinical trials, triglyceride levels fell below 500 mg/dL, an important threshold for reducing health risks. The treatment reduces a protein called apolipoprotein C-III, which is linked to high triglycerides. Specifically, studies have demonstrated that levels of this protein decreased by over 95%, resulting in a substantial drop in triglycerides. Most patients achieved safer triglyceride levels, highlighting the treatment’s potential effectiveness. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• ARO-APOC3
• Placebo

How Is the Trial Designed?

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+

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]

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]

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. 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 ... Arrowhead Presents New Clinical Data on ARO-APOC3 at AHA 2021 · APOC3 was reduced by 98% in FCS patients and 96% in MCM patients · Both groups showed similar ...

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

RNA Interference Therapy Targeting Apolipoprotein C-III in ... ARO-APOC3, a hepatocyte-targeting RNA interference therapeutic, inhibits APOC3 messenger ribonucleic acid expression, lowering triglyceride levels.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S193328742400148X

†Plozasiran (ARO-APOC3), an Investigational RNAi ... Reductions in APOC3 and TGs were –48% and -58% respectively at Wk48 (p <0.0001). The majority, 78% of patients achieved TGs <500 mg/dL by Wk48 vs >90% at Wk24.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06822790

Long-Term Safety and Efficacy of Plozasiran in Adults With ... This is an open-label study to be conducted in adults with hypertriglyceridemia (HTG) and severe hypertriglyceridemia (SHTG).

6. isrctn.com isrctn.com/ISRCTN12904794

A phase 3 study to evaluate the efficacy and safety of ARO- ... Less common side effects (<10%) include muscle pain, dizziness, abdominal pain, rash and abnormal sensation of the skin (tingling, pricking, chilling). Drugs ...

7. ahajournals.org ahajournals.org/doi/10.1161/circ.144.suppl_1.10357

Abstract 10357: ARO-APOC3, an Investigational RNAi ... ARO-APOC3 was safe, and consistently decreased APOC3, TG, and non-HDL-C, and increased HDL-C, regardless of underlying genetic cause of HTG.