Resumen

CKJX839D12303 es un estudio de investigación para determinar si el tratamiento en estudio, denominado inclisiran, en comparación con placebo administrado además de la medicación con estatinas, puede reducir eficazmente la cantidad total de placa formada en los vasos del corazón, medida mediante angiografía coronaria por tomografía computarizada (CCTA) desde el inicio hasta el mes 24. Este estudio se lleva a cabo en participantes elegibles con diagnóstico de enfermedad coronaria no obstructiva (ECNO), en la que las arterias coronarias tienen una obstrucción menor al 50%, y sin eventos cardiovasculares previos.

Descripción detallada

El propósito de este estudio es evaluar la eficacia de inclisiran comparado con placebo, administrado además de la dosis máxima tolerada de terapia con estatinas, para reducir el volumen total de ateroma coronario evaluado por CCTA en participantes con diagnóstico de enfermedad coronaria no obstructiva (ECNO) sin eventos cardiovasculares previos, que tengan un LDL-C ≥55 mg/dL (1,4 mmol/L), sin caída significativa de presión en la reserva fraccional de flujo calculada por tomografía computarizada (FFRct) y un puntaje de Leaman adaptado a TC \>5, a pesar del uso de la dosis máxima tolerada de terapia con estatinas (y, si corresponde, otro tratamiento hipolipemiante [THL] además de la terapia con estatinas durante al menos 30 días en hasta el 20% de los participantes aleatorizados).

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 80 YearsSexo: ALL

Criterios de inclusión

Male or female ≥18 years or ≤80 years of age at signing of informed consent.
Fasting LDL-C local lab value at the Screening Visit of either i) ≥100 mg/dL (2.6 mmol/L) if on statin therapy but not on a maximally tolerated statin therapy; ii) ≥150 mg/dL (3.9mmol/L) if statin naive and without documented statin intolerance; or iii) ≥55 mg/dL (1.4 mmol/L) if on a stable (≥4 weeks) dose of maximally tolerated statin therapy or if statin intolerant.
Fasting LDL-C local lab value ≥55 mg/dL (1.4 mmol/L) at the assessment performed during the Statin Optimization Period 3 Visit for participants going through the Statin Optimization Period.
Participants having NOCAD without previous cardiovascular events: NOCAD is defined as:.
Participant with CT-adapted Leaman score \>5. and a diameter stenosis \<50% or
Participants with a CT-adapted Leaman score \>5, a diameter stenosis ≥50% but with FFRCT ≥0.76.
At the Baseline Visit, participants must be on a stable (≥4 weeks) dose of maximally tolerated statin therapy. Participants not on maximally tolerated statin therapy and who do not have documented statin intolerance can be screened but must enter the study via a Statin Optimization Period.
Fasting LDL-C lab value ≥55 mg/dL (1.4 mmol/L) at the Baseline Visit, measured at the central laboratory. If the Baseline and Screening Visits occur on the same day, then the LDL-C assessment will be assessed on the central laboratory sample. If a participant qualifies at Screening but the fasting central lab LDL-C value at the Baseline visit does not meet eligibility, then eligibility will be determined based on the central lab result.
Fasting triglycerides value \<400 mg/dL (4.52 mmol/L) based on the local lab results at the Screening visit and on the central lab results at the CCTA visit.

Criterios de exclusión

Previous cardiovascular events history including myocardial infarction (MI), or prior coronary revascularization \[percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG)\].
Planned revascularization (PCI) or (CABG).
Previous cerebrovascular events including:
Prior ischemic stroke thought not to be caused by atrial fibrillation, valvular heart disease or mural thrombus.
History of prior percutaneous or surgical carotid artery revascularization.
History of Peripheral Artery Disease (PAD):
Prior documentation of a resting ankle-brachial index \<0.85.
History of prior percutaneous or surgical revascularization of an iliac, femoral, or popliteal artery.
Prior non-traumatic amputation of a lower extremity due to peripheral artery disease.
Cardiac disorders, including any of the following:
Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia, atrial fibrillation) within 3 months prior to randomization that is not controlled by medication or via ablation at the time of the Screening Visit.
Complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third-degree AV block) prior to randomization.
Contraindication for CCTA (e.g., allergic reactions to the contrast dye) or CCTA not meeting entry standards after two attempts during the Baseline CCTA Visit as assessed by the Imaging Core Lab.
Pacemaker or implantable cardioverter-defibrillator (ICD) in situ.
Systolic Left Ventricle Ejection Fraction \<30% at the Screening Visit.
Uncontrolled severe hypertension: systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg prior to randomization (assessed at the Screening Visit) despite antihypertensive therapy.
Heart failure New York Heart Association (NYHA) class III or class IV at the Screening Visit.
Renal insufficiency (eGFR \<30 mL/min/1.73m2) as measured by the Modification of Diet in Renal Disease (MDRD) formula at the Screening Visit and at the Statin Optimization 3 Visit.
Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver at the Screening Visit.
Local creatine kinase (CK) values of either, unless a more stringent threshold is mandated by a local regulatory authority
Local CK values ≥5x ULN at the Statin Optimization 3 Visit unless a more stringent threshold is mandated by a local regulatory authority
Participant with myopathy at the Statin Optimization 3 Visit.

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Inclisiran sodium 300 mg

Placebo

Ubicaciones

Novartis Investigative Site

Novartis Investigative Site

Patrocinadores