Non-obstructive coronary artery disease MedDRA version: 20.0 Level: PT Classification code 10011078 Term: Coronary artery disease System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Trade Name: Leqvio 284 mg solution for injection in pre-filled syringe
Product Name: Inclisiran
Product Code: [KJX839]
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed
Sponsors
NOVARTIS PHARMA AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent must be obtained before any assessment is performed. 2. Male or female =18 years or =80 years of age at signing of informed consent. 3. 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. 4. 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% but Fractional Flow Reserve (FFR) >0.8 by special wire measurement (CCTA or coronary angiography) 5. 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. 6. Participants having 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. *=NOCA is defined as the presence of coronary artery plaque with visual diameter stenosis 0.8 and CT-adapted Leaman score >5, which will be assessed by the Imaging Core Lab. 7. 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 330 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 270
Exclusion criteria
Exclusion criteria: 1. Previous 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 ischemic cerebrovascular event 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. 4. History of Peripheral Artery Disease (PAD): • Prior documentation of a resting ankle-brachial index 50% but FFR 180 mmHg or diastolic blood pressure >110 mmHg prior to randomization (assessed at the Screening Visit) despite antihypertensive therapy. 11. Heart failure New York Heart Association (NYHA) class III or class IV at the Screening Visit. 12. 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. 13. Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver at the Screening Visit. Participants who enter the Statin Optimization Period must have AST and ALT =3x ULN (as defined by local laboratory reference ranges collected at the Screening Visit) and reported by the Statin Optimization Telephone Visit 1 to be allowed to continue in the Statin Optimization Period. Please refer to Section 5.2 of the study protocol for the complete list of exclusion criteria
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Inclisiran compared to placebo, on top of maximally tolerated statin therapy, in reducing the total coronary atheroma volume assessed by CCTA from baseline to month 24;Secondary Objective: - Inclisiran compared to placebo, administered on top of maximally tolerated statin therapy, in reducing the LDL-C from baseline to month 24 - Inclisiran compared to placebo in percentage change in low attenuation plaque volume evaluated by CCTA - Inclisiran compared to placebo in percentage of participants experiencing progression, regression, or no change of total plaque atheroma volume (progression, regression, or no change will be defined in the SAP);Primary end point(s): Percentage change from baseline to month 24 in total coronary atheroma volume;Timepoint(s) of evaluation of this end point: From baseline to month 24. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: From baseline to month 24.;Secondary end point(s): -percentage change in LDL-C from baseline to month 24 -percentage change in low attenuation plaque volume evaluated by CCTA -percentage of participants with progression, regression, or no change of total plaque atheroma volume | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Chile, China, France, Germany, Hungary, India, Ireland, Italy, Japan, Korea, Republic of, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactRegulatory Affairs
Novartis Farma S.p.A.
Outcome results
None listed