ARO-ANG3 Injection for Homozygous Familial Hypercholesterolemia

(Gateway Trial)

Not currently recruiting at 14 trial locations

Overseen By Robert Rosenson, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Arrowhead Pharmaceuticals

Must be taking: Lipid lowering therapy

Must not be taking: siRNA, Antisense oligonucleoside, Evinacumab, Corticosteroids

Disqualifiers: Uncontrolled diabetes, Endocrine disease, 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

Duration: 36 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new injection called ARO-ANG3 to determine its safety and effectiveness for people with homozygous familial hypercholesterolemia (HoFH), a genetic condition causing extremely high cholesterol levels. Participants will receive two different doses of the treatment to evaluate its efficacy and safety over 36 weeks. Individuals diagnosed with HoFH, who have high cholesterol despite cholesterol-lowering treatments, and who are willing to follow a heart-healthy diet might be suitable for this study. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant medical advancements.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop your current medications, but you must be on stable lipid-lowering therapy. Some medications, like certain RNA treatments and evinacumab, are not allowed.

Is there any evidence suggesting that ARO-ANG3 Injection is likely to be safe for humans?

Research has shown that ARO-ANG3 is generally safe for people. In earlier studies, researchers administered this treatment in both single and repeated doses. Participants did not experience any major safety problems. Some minor side effects occurred, but they were neither serious nor long-lasting. These results suggest that ARO-ANG3 injections are safe for humans when used in controlled settings. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for Homozygous Familial Hypercholesterolemia, which often involves a combination of statins, PCSK9 inhibitors, and other lipid-lowering drugs, ARO-ANG3 offers a fresh approach by targeting the ANGPTL3 protein, a key regulator of lipid metabolism. This new mechanism of action has the potential to reduce LDL cholesterol levels more effectively. Additionally, ARO-ANG3 is administered subcutaneously, which could offer a more convenient dosing option compared to some traditional treatments. Researchers are particularly excited about its potential to provide significant cholesterol reduction for patients who may not respond adequately to current therapies.

What evidence suggests that ARO-ANG3 Injection might be an effective treatment for homozygous familial hypercholesterolemia?

Research has shown that ARO-ANG3 may help lower LDL-C, often called "bad" cholesterol, which is important for treating homozygous familial hypercholesterolemia (HoFH). Early studies with healthy participants showed a significant drop in LDL-C levels, between 45% and 54%, after receiving ARO-ANG3 injections. In animal studies, cholesterol levels dropped by an impressive 98% without major side effects, suggesting potential effectiveness. This trial will test different doses of ARO-ANG3 to evaluate its effectiveness and safety in managing HoFH, a condition that causes very high cholesterol levels from a young age. ^{2 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals with a severe form of high cholesterol called homozygous familial hypercholesterolemia (HoFH). Participants must be on stable cholesterol-lowering therapy, not have heart disease symptoms or uncontrolled diabetes, and agree to use effective contraception. They should also follow a low-fat diet and have LDL-C levels over 100 mg/dL.

Inclusion Criteria

Willing to provide written informed consent and to comply with study requirements

I am on a stable dose of the highest safe cholesterol medication.

Participants of childbearing potential (males & females) must agree to use highly-effective contraception during the study and for at least 24 weeks from the last dose of study medication

Exclusion Criteria

Your fasting triglyceride levels are higher than 300 mg/dL when tested before the study.

I have a hormone-related condition affecting my cholesterol or fat levels.

I was diagnosed with diabetes in the last 3 months or my diabetes is not well-controlled (HbA1c > 9%).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 2 open-label doses of ARO-ANG3 and are evaluated for safety and efficacy parameters

36 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants may opt to continue in an additional 24-month extension period receiving up to 8 doses of ARO-ANG3

24 months

What Are the Treatments Tested in This Trial?

Interventions

• ARO-ANG3 Injection

Trial Overview The study tests ARO-ANG3 injections in people with HoFH. It involves two initial doses followed by safety and effectiveness checks over 36 weeks. Those who finish can join a further 24-month extension for up to eight more doses.

How Is the Trial Designed?

Group I: ARO-ANG3 Dose 2 Experimental Treatment 1 Intervention

ARO-ANG3 Dose Level 2 SC

Group II: ARO-ANG3 Dose 1 Experimental Treatment 1 Intervention

ARO-ANG3 Dose Level 1 subcutaneous (SC)

Who Is Running the Clinical Trial?

Arrowhead Pharmaceuticals

Lead Sponsor

Trials

45

Recruited

6,200+

Citations

1. arrowheadpharma.com arrowheadpharma.com/news-press/arrowhead-pharmaceuticals-initiates-phase-2-gateway-study-of-investigational-aro-ang3-for-treatment-of-homozygous-familial-hypercholesterolemia/

Arrowhead Pharmaceuticals Initiates Phase 2 GATEWAY ... The GATEWAY Phase 2 clinical study will evaluate efficacy and safety in patients with HoFH, so we can assess the potential of ARO-ANG3 to be a new treatment ...

2. 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 ...

3. clinicaltrial.be clinicaltrial.be/en/details/33544?per_page=20&only_recruiting=0&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_eligible=0&only_active=0

Study of ARO-ANG3 in Participants With Homozygous ... Phase 2 Study to Evaluate the Safety and Efficacy of ARO-ANG3 in Subjects With Homozygous Familial Hypercholesterolemia (HOFH). Active, not ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9371762/

Advancements in the Treatment of Homozygous Familial ... Early results from healthy volunteers following dose-varying subcutaneous injections of ARO-ANG3 on days 1 and 29 showed a 45%–54% decrease in LDL-C at 4–6 ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2589004224018662

Recent progress in gene therapy for familial ... Remarkably, they observed a 98% reduction in cholesterol levels and no significant side effects in the mice, suggesting promise for this ...

6. ir.arrowheadpharma.com ir.arrowheadpharma.com/news-releases/news-release-details/arrowhead-presents-interim-data-aro-ang3-phase-2-gateway-study

Arrowhead Presents Interim Data from ARO-ANG3 Phase 2 ... The AROANG3-2003 GATEWAY study (NCT05217667) is a Phase 2 open-label study to evaluate the efficacy, safety, and tolerability of 200 mg and 300 mg of ARO-ANG3 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11698773/

Homozygous Familial Hypercholesterolemia Treatment LDLC reduction in patients on apheresis was 18.1% at week 12. Safety results in the 14 adolescent participants did not differ from adult ...

8. nature.com nature.com/articles/s41591-023-02494-2

RNA interference targeting ANGPTL3 for triglyceride and ... Overall safety. ARO-ANG3 was generally well tolerated when administered subcutaneously as a single dose in HPs and repeat doses in HPs and ...