Recruiting NCT07000357

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

Phase III Interventional Cardiovascular Disease

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: AZD0780, Placebo.
Who it may be relevant to: Registry conditions: Cardiovascular Disease. Basic parameters: from 18 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Argentina, Brazil, Bulgaria, Canada +31
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

A Phase III, Randomised, Double-blind, Placebo-controlled, Parallel-group Study to Assess the Effect of AZD0780 on Major Adverse Cardiovascular Events in Patients With Established Atherosclerotic Cardiovascular Disease (ASCVD) or at High Risk for a First ASCVD Event

Overview

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.

Interventions

Drug AZD0780
Participants will receive oral AZD0780 once daily
Drug Placebo
Participants will receive oral placebo once daily

Primary outcome measures

Time to first event of any component of MACE-PLUS [Time frame: Up to approximately 54 months]

Secondary outcome measures (7)

Time to first event of any component of 3P MACE [Time frame: Up to approximately 54 months]
Time to first event of any component of MACE PLUS [Time frame: Up to approximately 54 months]
Time to first event of MI [Time frame: Up to approximately 54 months]
Time to first event of urgent coronary revascularisation [Time frame: Up to approximately 54 months]
Time to CV death [Time frame: Up to approximately 54 months]
Time to first event of MALE [Time frame: Up to approximately 54 months]
Time to all-cause mortality [Time frame: Up to approximately 54 months]

Eligibility criteria

Inclusion criteria

Meets one of the following:

Participants with history of an ASCVD event: Participants ≥ 18 years of age at the time of signing the ICF with a history of MI or ischaemic stroke suspected to be due to atherosclerotic vascular disease ≥ 1 month prior to randomisation (presumed lacunar or cardioembolic strokes are not qualifying events), or revascularisation for symptomatic lower limb PAD any time prior to screening

Additional risk factors based on the level of the LDL-C and timing of MI or stroke:

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.

ii) T2DM requiring ongoing medical therapy iii) Age ≥ 65 years v) Previous above ankle amputation due to PAD vi) Previous diagnosis of non-end stage CKD

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), with no prior history of MI, ischaemic stroke due to atherosclerotic disease, or leg revascularisation for symptomatic lower limb PAD, and with 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 at least one of the following end-organ diseases:

Nephropathy - Persistent (≥ 2 readings) microalbuminuria (urine albumin/creatinine ratio ≥ 30 mg/g) and/or persistent eGFR < 60 mL/min/1.73 m2. At least one reading must come from the medical record within the last 12 months in addition to the reading from screening
Retinopathy - Treated diabetic retinopathy (surgical intervention or injectable therapy) or prior diagnosis made by a relevant healthcare specialist
Neuropathy - Treated neuropathy (medical therapy for pain relief or symptom alleviation) or prior diagnosis made by a relevant healthcare specialist
ABI < 0.9 or > 1.4 - confirmed either in study during screening or randomisation, or from the medical record within the last 5 years (iii) Documented atherosclerosis of less significance

For (ii) and (iii), participants need to have at least one of the additional risk factors below:

CKD with eGFR x mL/min/1.73 m2
Current tobacco use
Age ≥ 65
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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Randomized
Model: Parallel assignment
Masking: Quadruple blind
Primary purpose: Treatment