Resumen

El objetivo de este estudio de fase 3, aleatorizado, controlado con placebo, dirigido por eventos, es evaluar el efecto de AZD0780, un inhibidor oral de PCSK9, en comparación con placebo para reducir el riesgo de MACE-PLUS en pacientes con ASCVD establecida o con alto riesgo de un primer evento de ASCVD. El efecto de AZD0780 frente a placebo sobre el riesgo de MACE-PLUS se evaluará desde la aleatorización hasta la fecha de cierre del análisis primario (PACD). La visita de cierre del estudio se programará para realizarse después de la PACD y será la visita final de cada participante en el estudio.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

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 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
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:
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.

Criterios de exclusión

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.

Ubicaciones

Research Site

CABA, Argentina

RECRUITING

Research Site

CABA, Argentina

RECRUITING