AZD0780 for Hypercholesterolemia

(AZURE-HeFH Trial)

Recruiting at 140 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: Statins, Ezetimibe

Must not be taking: Mipomersen, Lomitapide, Gemfibrozil, PCSK-9 inhibitors

Disqualifiers: Homozygous FH, Uncontrolled diabetes, 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: 2

Duration: 52 weeks

405 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called AZD0780, a potential cholesterol-lowering drug, to determine if it can safely reduce bad cholesterol (LDL-C) levels in individuals with HeFH, a genetic condition that causes high cholesterol. The trial compares AZD0780 to a placebo (a pill with no active medicine) to thoroughly understand its effects. Eligible participants should have HeFH, be on a stable cholesterol-lowering medication plan, and still have high LDL-C levels. Participants will take either AZD0780 or the placebo daily and will be involved in the study for a little over a year. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for high cholesterol.

Will I have to stop taking my current medications?

You will need to be on a stable dose of your current cholesterol-lowering medications, like statins, for at least 28 days before joining the study. Some specific medications, like mipomersen, lomitapide, gemfibrozil, and certain PCSK-9 inhibitors, cannot be used before or during the study.

Is there any evidence suggesting that AZD0780 is likely to be safe for humans?

A previous study found AZD0780 to be safe and well-tolerated, meaning most participants did not experience major side effects. The treatment was gentle on patients' bodies.

Research also showed that eating food increased the amount of AZD0780 in the body by about 30%. This increase does not appear to cause any serious problems, but it is something to be aware of. Overall, based on the available data, the treatment appears safe for humans. ^{1 2 3 4 5}

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

Unlike the standard cholesterol treatments like statins, AZD0780 is unique because it targets a different pathway in the body to lower cholesterol levels. Most treatments work by blocking enzymes in the liver, but AZD0780 works by modulating a receptor that plays a key role in cholesterol absorption. This new mechanism of action could potentially offer a more effective and faster-acting option for people who don't respond well to existing therapies. Researchers are excited because this could mean better outcomes for patients struggling with high cholesterol.

What evidence suggests that AZD0780 might be an effective treatment for hypercholesterolemia?

Research has shown that AZD0780, which participants in this trial may receive, is a promising treatment for lowering "bad" cholesterol, known as LDL-C. In earlier studies, AZD0780, a type of medication called a PCSK9 inhibitor, reduced LDL-C by up to 50.7% after 12 weeks. This suggests it could significantly lower cholesterol in people with high levels. Additionally, about 84% of participants in that study reached their cholesterol goals with this treatment. The drug is also considered safe, as it doesn't cause many serious side effects. These findings suggest AZD0780 could effectively help manage high cholesterol. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults with hereditary high cholesterol (HeFH) who either have heart disease and LDL ('bad') cholesterol levels of 55 mg/dL or higher, or don't have heart disease but their LDL levels are 70 mg/dL or higher. Specific eligibility details were not provided.

Inclusion Criteria

Participants judged not to tolerate high intensity statins may be included under certain conditions

I am on the highest dose of cholesterol medication that I can tolerate.

Fasting serum LDL-C levels as specified based on HeFH status and clinical ASCVD

Exclusion Criteria

I am currently taking or plan to take cholesterol-lowering medication.

Specific abnormal laboratory values at screening

I have a genetic condition that causes very high cholesterol.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Treatment

Participants receive AZD0780 or placebo daily for 52 weeks

52 weeks

Regular visits (frequency not specified)

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 days

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• AZD0780

Trial Overview The study tests AZD0780, a drug intended to lower LDL cholesterol, against a placebo in a blind setup where neither participants nor investigators know who's receiving the actual medication. The study spans up to 56 weeks including screening, treatment, and follow-up.

How Is the Trial Designed?

Group I: AZD0780 Experimental Treatment 1 Intervention

Participants will receive daily oral dose of AZD0780

Group II: Placebo Placebo Group 1 Intervention

Participants will receive daily oral dose of placebo

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Citations

1. astrazeneca.com astrazeneca.com/content/astraz/media-centre/press-releases/2025/azd0780-a-novel-oral-pcsk9-inhibitor-demonstrated-significant-ldl-cholesterol-ldl-c-reduction-in-pursuit-phase-iib-trial.html

AZD0780, a novel oral PCSK9 inhibitor, demonstrated ... In addition, AZD0780 30mg enabled 84% [95%CI: 74.4%-90.7%] of trial participants to meet their American Heart Association/American College of ...

2. jacc.org jacc.org/doi/10.1016/j.jacc.2025.03.499

An Oral PCSK9 Inhibitor for Treatment of ... Broadly speaking, AZD0780 led to lipid-lowering effects that reflect expectations for an effective inhibitor of PCSK9 with peak LDL-C effects of ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40167413/

An Oral PCSK9 Inhibitor for Treatment of ... AZD0780 demonstrated robust, dose-dependent reductions in LDL-C with a favorable safety and tolerability profile supporting further ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT07000136

A Phase III Study to Assess the Effect of AZD0780 on LDL- ... This is a study to evaluate the efficacy and safety of AZD0780 in adults with HeFH and elevated LDL-C, either with clinical ASCVD and LDL-C levels of 55 ...

5. pace-cme.org pace-cme.org/news/phase-2b-results-of-oral-pcsk9-inhibitor-in-hyperlipidemia/2473976/

Phase 2b results of oral PCSK9 inhibitor in hyperlipidemia AZD0780, an investigational oral small molecule PCSK9 inhibitor, reduced LDL-c by up to 50.7% at 12 weeks in patients with hyperlipidemia, compared with ...

6. atherosclerosis-journal.com atherosclerosis-journal.com/article/S0021-9150(24)01081-5/fulltext

AZD0780, the first oral small molecule PCSK9 inhibitor for ... Results: No serious adverse events were reported. Based on preliminary data, food increased total exposure approximately 30% compared to dosing when fasting.