Coronary computed tomography study to assess the effect of inclisiran on atherosclerotic plaque progression in participants with a diagnosis of nonobstructive coronary artery disease without previous cardiovascular events

JRCT ID: jRCT2071230017

Registered date:28/05/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Coronary Artery Disease
• Date of first enrollment: 21/06/2023
• Target sample size: 5
• Countries of recruitment: United States,Japan,Argentina,Japan,Belgium,Japan,Brazil,Japan,Canada,Japan,Chile,Japan,China,Japan,France,Japan,Hungary,Japan,India,Japan,Ireland,Japan,Italy,Japan,Korea, Republic of,Japan,Spain,Japan,Switzerland,Japan,United Kingdom,Japan
• Study type: Interventional

Intervention(s)

Arm1:300 mg inclisiran sodium Subcutaneous injection
Arm2:Placebo Subcutaneous injection

Outcome(s)

• Primary Outcome: Percentage change in total coronary atheroma volume

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 80age old
• Gender: Both

Include criteria

1. Fasting LDL-C local lab value at the Screening Visit of either i) >=100 mg/dL if on statin therapy but not on a maximally tolerated statin therapy; ii) >=150 mg/dL if statin naive and without documented statin intolerance; or iii) >=70 mg/dL if on a stable (>=4 weeks) dose of maximally tolerated statin therapy or if statin intolerant.
2.Participants may be pre-identified based on a CCTA or an invasive angiography that is performed as part of standard of care within 12 months prior to the participant's Screening Visit demonstrating:
Presence of coronary artery plaque with visual diameter stenosis <50% or
Coronary artery plaque with visual artery stenosis >50% but Fractional Flow Reserve (FFR) >0.8 by special wire measurement (CCTA or coronary angiography)
3.Fasting LDL-C local lab value >=70 mg/dL at the assessment performed during the Statin Optimization Period 3 Visit for participants going through the Statin Optimization Period.
4.Participants having Non-Obstructive Coronary Artery (NOCA) confirmed by CCTA with FFRct >0.8 and CT-adapted Leaman score >5 or coronary artery plaque with visual diameter stenosis >50% but with FFRct >0.8 and CT-adapted Leaman score >5 without previous cardiovascular events.
A standard of care CCTA may serve as the study baseline CCTA scan if it is performed within 3 months prior to the participant's Screening Visit and meets the inclusion criteria of FFRct >0.8 and CT-adapted Leaman score >5, which will be assessed by the Imaging Core Lab.
5.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.

Exclude criteria

1.Previous cardiovascular events history including myocardial infarction (MI), or prior coronary revascularization [percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG)].
2.Planned revascularization (PCI) or (CABG).
3.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.
4.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.
5.NOCA participant who was prescreened by the Investigator with visual diameter stenosis >50% but FFR <0.8.
6.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.
7.Pacemaker or implantable cardioverter-defibrillator (ICD) in situ.
8.Systolic Left Ventricle Ejection Fraction <30% at the Screening Visit.
9.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.
10.Heart failure New York Heart Association (NYHA) class III or class IV at the Screening Visit.
11.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.
12.Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver at the Screening Visit.

Related Information

• Primary Sponsor: Hirano Takamitsu
• Secondary ID(s): NCT05360446