AZD0780 for Cardiovascular Disease

(AZURE-LDL Trial)

Recruiting at 345 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: Statins

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

Disqualifiers: Homozygous familial hypercholesterolaemia, 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

2800 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, which aims to lower LDL-C (bad cholesterol) levels in the blood. Researchers seek to determine if this treatment is safe and effective for individuals with or at risk of developing heart disease (ASCVD). Participants will receive either the actual treatment or a placebo (a non-active pill) without knowing which one they receive. The study seeks adults with a history of heart-related issues or those at risk of a first heart event who have high LDL-C levels despite taking cholesterol-lowering medications. 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 heart disease.

Will I have to stop taking my current medications?

You may need to stop certain cholesterol-lowering medications like mipomersen, lomitapide, gemfibrozil, and PCSK-9 inhibitors before joining the trial. However, you should continue your current statin or lipid-lowering regimen if it's stable and tolerated.

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

Earlier studies have shown that AZD0780 lowers LDL-C, the "bad" cholesterol in the blood. Research indicates that patients tolerated the treatment well, with no major safety issues reported. Some experienced mild side effects, but these were not serious. The treatment is a daily pill, making it easy to use. AZD0780 is now in advanced testing stages, indicating that earlier trials found it safe for use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for cardiovascular disease, which often include beta-blockers, ACE inhibitors, or statins, AZD0780 is unique because it introduces a new active ingredient targeting a specific pathway involved in cardiovascular health. Researchers are excited about AZD0780 because it offers a novel mechanism of action that could potentially improve heart function more effectively than existing options. This treatment stands out for its potential to provide better outcomes for patients who do not respond well to current therapies.

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

Research has shown that AZD0780, a pill that lowers cholesterol, can significantly reduce levels of "bad" cholesterol in the blood. In a previous study, 84% of people taking AZD0780 reached their cholesterol targets set by major heart health organizations. Participants in this trial will receive either AZD0780 or a placebo. AZD0780 functions like other cholesterol-lowering drugs but offers the added convenience of being taken as a pill, making it a promising option for those at risk of heart disease. Early results also suggest that AZD0780 is generally safe for patients. ^{2 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with clinical atherosclerotic cardiovascular disease (ASCVD) or those at risk of their first ASCVD event, who also have high levels of LDL cholesterol ('bad' cholesterol). Participants must not know if they're getting the actual drug or a placebo.

Inclusion Criteria

My LDL cholesterol level meets the required range for my heart disease risk.

I am 18 years old or older.

I have a history of heart or artery disease, or I'm at risk due to conditions like diabetes, high blood pressure, smoking, kidney disease, or obesity.

Exclusion Criteria

Homozygous familial hypercholesterolaemia, known diagnosis of HeFH, LDL apheresis or plasma apheresis within 12 months prior to screening, or any other underlying known disease or condition that may interfere with interpretation of the clinical study results as judged by the Investigator.

I haven't used PCSK-9 inhibitors recently and don't plan to during the study.

Any of the following laboratory values at screening: Calculated eGFR < 15 mL/min/1.73 m2, AST or ALT > 3 × ULN, TBL > 2 × ULN (except for patients with Gilberts syndrome, where TBL 3 × ULN is acceptable provided direct bilirubin < 1.5 × ULN, Fasting triglycerides ≥ 400 mg/dL (≥ 4.52 mmol/L), Creatine kinase > 5 × ULN, Urine albumin-to-creatinine ratio ≥ 500 mg/g

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 once 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 molecule designed to lower LDL-C in the blood. It's compared against a placebo in a double-blind setup where neither participants nor investigators know who receives which treatment until the study ends after about 56 weeks.

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

An Oral PCSK9 Inhibitor for Treatment of ... The phase 2 PURSUIT study showed a favorable efficacy and safety profile of AZD0780, broadly comparable to other PCSK9 inhibitors, with the ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07000357

NCT07000357 | A Phase III Study of AZD0780 on Major ... The purpose of this phase 3, randomized, placebo controlled, event-driven study is to assess the effect of AZD0780, an oral PCSK9 inhibitor, compared with ...

3. 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 ...

4. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D7960C00012

A Phase III study to assess the effect of AZD0780 on LDL-C ... This is a study to evaluate the efficacy and safety of AZD0780 in adults with clinical ASCVD or who are at risk for a first ASCVD event and who have elevated ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0735109725059078

An Oral PCSK9 Inhibitor for Treatment of ... The phase 2 PURSUIT study showed a favorable efficacy and safety profile of AZD0780, broadly comparable to other PCSK9 inhibitors, with the advantage of a once- ...

6. astrazeneca-us.com astrazeneca-us.com/media/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 ... Data from PURSUIT are consistent with Phase I findings for AZD0780 which demonstrated a statistically significant reduction of 51% in LDL-C ...

7. astrazeneca.com astrazeneca.com/content/astraz/media-centre/medical-releases/azd0780-an-oral-pcsk9-inhibitor-demonstrated-significant-ldl-c-reduction-on-top-of-statin-in-phase-i-trial.html

AZD0780, an oral PCSK9 inhibitor demonstrated ... The trial assessed the safety, tolerability, pharmacokinetics, and pharmacodynamics of AZD0780 in lowering low-density lipoprotein cholesterol ( ...

8. atherosclerosis-journal.com atherosclerosis-journal.com/article/S0021-9150(25)00486-1/fulltext

Efficacy and safety of AZD0780, an oral small molecule ... AZD0780, a once daily oral small molecule inhibitor of PCSK9 may provide a promising therapy for LDL-C lowering when administered on top of standard of care or ...