A Phase III Study of AZD0780 on Major Adverse CV Events in Patients With a History of ASCVD Events or at High Risk for a First Event (AZURE-Outcomes)

AstraZeneca

Status and phase: Enrolling; Phase 3

Conditions: Cardiovascular Disease

Treatments: Drug: AZD0780; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT07000357

D7960C00015

2025-520519-14 (Registry Identifier)

Details and patient eligibility

About

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 placebo in reducing the risk of MACE-PLUS in patients with established ASCVD or at high risk for a first ASCVD event. The effect of AZD0780 vs placebo on the risk of MACE-PLUS will be evaluated from randomisation until the primary analysis censoring date (PACD). The Study Closure Visit will be scheduled to occur after the PACD and will be the final visit for each participant in the study.

Enrollment: 15,100 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Meets one of the following:

  1. 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:

     • 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

  2. 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:

1. CKD with eGFR x mL/min/1.73 m2

2. Current tobacco use

3. Age ≥ 65

4. T2DM (if included on the less significant atherosclerosis criterion iii)

   • 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

• 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.

• Any revascularisation procedure planned within the next 3 months.

• Available imaging assessment within the last 3 years showing either coronary calcium score of zero, or a coronary computed tomography angiography with no atherosclerosis.

• Calculated eGFR < 15 mL /min/1.73 m2 at screening.

• 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

• Uncontrolled T2DM defined as HbA1c ≥ 9.5% at screening.

• 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.

• Use of mipomersen or lomitapide (cholesterol-lowering medications) within 12 months of screening or planned use during the study.

• Use of gemfibrozil within one week prior to the Screening Visit or planned use during the study.

• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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15,100 participants in 2 patient groups, including a placebo group

AZD0780

Experimental group

Description:

Participants will receive oral AZD0780 once daily

Treatment:

Drug: AZD0780

Placebo

Placebo Comparator group

Description:

Participants will receive oral placebo once daily

Treatment:

Drug: Placebo