A Trial to Test How AZD0780 Affects Serious Heart, Stroke, or Vascular Problems in Patients with Heart, Stroke or Vascular Disease or at High Risk for Such Issues

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

3 Sep 2025 → ongoing

Decision date (initial)

2025-08-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Pharmacodynamic, Efficacy

To compare the effect of treatment with AZD0780 to placebo in reducing the risk of MACE-PLUS (the composite of cardiovascular [CV] death, myocardial infarction [MI], ischaemic stroke, acute lower limb ischaemia, major amputation of a vascular aetiology, and urgent arterial revascularisation)

Secondary objectives 7

1. To compare the effect of treatment with AZD0780 to placebo in reducing the risk of 3-point (3P)-MACE (the composite of CV death, MI, and ischaemic stroke)
2. To compare the effect of treatment with AZD0780 to placebo in reducing the risk of MACE-PLUS in patients with a history of ASCVD
3. To compare the effect of treatment with AZD0780 to placebo in reducing the risk of MI
4. To compare the effect of treatment with AZD0780 to placebo in reducing the risk of urgent coronary revascularization
5. To compare the effect of treatment with AZD0780 to placebo in reducing the risk of CV death
6. To compare the effect of treatment with AZD0780 to placebo in reducing the risk of major adverse limb event (MALE) (the composite of acute lower limb ischemia, major amputation of vascular aetiology, and urgent lower extremity revascularisation)
7. To compare the effect of treatment with AZD0780 to placebo in reducing the risk of all-cause mortality

Conditions and MedDRA coding

Atherosclerotic Cardiovascular Disease

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. Meets one of the following: (a) Participants with history of an ASCVD event: Participants ≥ 18 years of age at the time of signing the ICF with a history of ASCVD defined as ACS ≥ 1 month to ≤ 12 months prior to randomisation, ischaemic stroke suspected to be due to atherosclerotic vascular disease ≥ 1 month to ≤ 12 months prior to randomisation, or revascularisation for symptomatic lower limb PAD any time prior to screening Additional risk factors based on the level of the LDL-C: o Participants with an LDL-C ≥ 75 mg/dL (≥ 1.9 mmol/L) need to have at least one of the other additional risk factors (i to viii) below. i) T2DM requiring ongoing medical therapy ii) Age ≥ 65 years v) Previous above ankle amputation due to PAD vi) Previous diagnosis of non-end stage CKD (b) Participants at increased risk of a first ASCVD event: Male participant ≥ 50 years of age or female participant ≥ 55 years of age at the time of signing the ICF with LDL-C ≥ 100 mg/dL (≥ 2.6 mmol/L) and diagnostic evidence of at least one of the following disease categories (i, ii, or iii): i) Significant atherosclerotic artery disease ii) High-risk Type 1 or Type 2 diabetes mellitus with manifestation of end-organ disease (diabetic nephropathy, retinopathy, neuropathy or an ABI outside the normal range [0.9 to 1.4]) iii) Documented atherosclerosis of less significance For (ii) and (iii), participants need to have at least one of the additional risk factors below: a) CKD with eGFR x mL/min/1.73 m2 b) Current tobacco use c) Age ≥ 65 d) T2DM (if included on the less significant atherosclerosis criterion iii)
2. Participants should receive a background lipid lowering regimen anticipated to achieve at least a ~50% reduction in LDL-C. Except in cases of intolerance, the regimen should include a high intensity statin therapy or lower intensity statin therapy in combination with an oral agent with proven outcome benefit (eg, ezetimibe and/or bempedoic acid). Participants must achieve a stable background lipid lowering therapy > 28 days before screening.

Exclusion criteria 10

1. Any underlying known disease, or condition including homozygous familial hypercholesterolaemia, or LDL or plasma apheresis within 12 months prior to randomisation, that, in the opinion of the investigator, might interfere with the interpretation of the clinical study results.
2. Any revascularisation procedure planned within the next 3 months.
3. Available imaging assessment within the last 3 years showing either coronary calcium score of zero, or a coronary computed tomography angiography with no atherosclerosis.
4. Calculated eGFR < 15 mL/min/1.73 m2 (CKD-EPI formula; Delgado et al 2022, Inker et al 2021) at screening.
5. Any laboratory values with the following deviations at screening: - AST or ALT > 3 × ULN - TBL > 2 × ULN (except for participants with Gilbert's 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/creatinine ratio ≥ 500 mg/g
6. Uncontrolled T2DM defined as HbA1c ≥ 9.5% at screening.
7. Inadequately treated hypothyroidism defined as TSH > 1.5 × ULN at screening or participants whose thyroid replacement therapy was initiated or modified within the last 3 months prior to screening.
8. Use of mipomersen or lomitapide (cholesterol-lowering medications) within 12 months of screening or planned use during the study.
9. Use of gemfibrozil within one week prior to the Screening Visit or planned use during the study.
10. Use of PCSK9 inhibitors: evolocumab/alirocumab within 12 weeks of the Screening Visit or planned use during the study, or inclisiran within 18 months of the Screening Visit or planned use during the study, or any other approved PCSK9 inhibitor use within 5 half lives prior to the Screening Visit or planned use during the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time to first event of any component of MACE PLUS

Secondary endpoints 7

1. Time to first event of any component of 3P MACE
2. Time to first event of any component of MACE PLUS in participants with a prior history of ASCVD
3. Time to first event of MI
4. Time to first event of urgent coronary revascularisation
5. Time to CV death
6. Time to first event of MALE
7. Time to all-cause mortality

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

13 EU/EEA countries · 380 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 116 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

23 submissions — initial application plus substantial / non-substantial modifications