Zodasiran for Hypercholesterolemia

Recruiting at 2 trial locations

Overseen By Medical Monitor

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Arrowhead Pharmaceuticals

Must be taking: Lipid-lowering therapy

Must not be taking: Hepatocyte-targeted siRNA, Antisense oligonucleotides

Disqualifiers: Evinacumab, Investigational agents, 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: 10-12 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests zodasiran, a new treatment for individuals with Homozygous familial hypercholesterolemia (HoFH), a genetic condition that causes extremely high cholesterol levels. The study aims to evaluate the effectiveness and safety of zodasiran compared to a placebo. Participants will initially receive either zodasiran or a placebo, and later, everyone can choose to try zodasiran. The trial seeks individuals diagnosed with HoFH who are currently on cholesterol-lowering medication. As a Phase 3 trial, this is the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but you must be on standard lipid-lowering therapy. Some specific drugs are not allowed close to the trial start, like certain siRNA and antisense oligonucleotides.

Is there any evidence suggesting that zodasiran is likely to be safe for humans?

Research has shown that zodasiran is generally safe. In studies involving patients with high blood fat levels, zodasiran was well-tolerated and demonstrated a good balance of benefits and risks. No major safety issues have been reported, suggesting it is safe for humans. However, as with any treatment, monitoring for side effects during the trial is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for hypercholesterolemia?

Unlike the standard cholesterol treatments, which often include statins that work by inhibiting cholesterol synthesis in the liver, Zodasiran takes a novel approach. It targets the RNA involved in cholesterol production, aiming to reduce cholesterol levels more directly and potentially with fewer side effects. This RNA interference mechanism is relatively new in the treatment of hypercholesterolemia, making researchers excited about its potential for increased efficacy and safety compared to traditional therapies. Plus, its administration via subcutaneous injection offers a straightforward delivery method, which could improve patient compliance.

What evidence suggests that zodasiran might be an effective treatment for hypercholesterolemia?

Research has shown that zodasiran, which participants in this trial may receive, can help lower cholesterol levels. In studies, patients with homozygous familial hypercholesterolemia (HoFH), a condition causing very high cholesterol, experienced a reduction in "bad" cholesterol, known as LDL-C, after taking zodasiran. The treatment also reduced other substances linked to heart disease risk, such as apolipoprotein B and non-HDL cholesterol. Zodasiran targets a protein called ANGPTL3, which helps control blood fats. This approach has demonstrated lasting benefits in clinical trials. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for adolescents and adults aged 12 years or older with Homozygous Familial Hypercholesterolemia (HoFH), a genetic condition causing very high cholesterol levels. Participants must have either a genetic diagnosis or clinical signs of HoFH to join.

Inclusion Criteria

I am 12 years or older, not pregnant, not breastfeeding, and do not plan to become pregnant during the study.

I weigh at least 35 kg.

LDL-C ≥70 mg/dL (1.8 mmol/L)

Exclusion Criteria

I have not used evinacumab in the last 3 months.

My LDL-C levels did not drop by 15% after 2 doses of evinacumab.

I am not on steroids, except as a stable treatment for pituitary/adrenal issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 5 doses of zodasiran or placebo by subcutaneous injection during the double-blind treatment period

10-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment with 4 or 5 doses of zodasiran by subcutaneous injection

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Zodasiran

Trial Overview The study tests the effectiveness and safety of zodasiran, an injectable medication, compared to a placebo in reducing cholesterol levels. It's randomized, meaning participants are randomly assigned to receive either zodasiran or placebo without choice.

How Is the Trial Designed?

Group I: zodasiran Experimental Treatment 1 Intervention

5 doses of zodasiran by subcutaneous (sc) injection (randomized period). 4 or 5 doses of zodasiran by sc injection (optional open-label period).

Group II: Placebo Placebo Group 2 Interventions

Calculated volume to match active treatment by sc injection (randomized period). 4 or 5 doses of zodasiran by sc injection (optional open-label period)

Who Is Running the Clinical Trial?

Arrowhead Pharmaceuticals

Lead Sponsor

Trials

45

Recruited

6,200+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38809174/

Zodasiran, an RNAi Therapeutic Targeting ANGPTL3, for ... In patients with mixed hyperlipidemia, zodasiran was associated with significant decreases in triglyceride levels at 24 weeks.

2. atherosclerosis-journal.com atherosclerosis-journal.com/article/S0021-9150(25)01272-9/fulltext

Zodasiran (ARO-ANG3), an investigational RNAi ... Conclusions: Sustained reductions in LDL-C, apolipoprotein B and Lp(a) were achieved with quarterly dosing of zodasiran with similar nadir reductions as in the ...

3. ir.arrowheadpharma.com ir.arrowheadpharma.com/news-releases/news-release-details/arrowhead-pharmaceuticals-initiates-phase-3-yosemite-study

Arrowhead Pharmaceuticals Initiates Phase 3 YOSEMITE ... “In Phase 2 clinical studies, patients with HoFH receiving zodasiran achieved reductions from baseline in LDL-C, ApoB, non-HDL-C, and ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT07037771

A Phase 3 Study of Zodasiran in Adolescent and Adult ... This multicenter, randomized, placebo-controlled study will evaluate the efficacy and safety of zodasiran subcutaneous (SC) injection in subjects 12 years of ...

5. mediacenteratypon.nejmgroup-production.org mediacenteratypon.nejmgroup-production.org/NEJMoa2404147.pdf

Zodasiran, an RNAi Therapeutic Targeting ANGPTL3, for ... ANGPTL3 loss-of-function carriers have lower levels of triglycerides, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) ...

6. ir.arrowheadpharma.com ir.arrowheadpharma.com/static-files/d9630706-0c91-4c68-8332-2e767d022399

2 Year Open Label Extension (OLE) Results from ARCHES-2 For efficacy analysis on FAS, the number of patients are 51 in each group, for the safety analysis on safety population, the patients are 50, 51 ...

7. reports.mountsinai.org reports.mountsinai.org/article/card2025-_7_cholesterol

RNA Inhibitor Is Shown Safe and Effective in Reducing ... It evaluated the safety and efficacy of zodasiran in adults with mixed hyperlipidemia—with fasting triglyceride level of 150 to 499 mg per deciliter and ...