Inclisiran (inclisiran sodium) for Non-obstructive coronary artery disease

Inclusion criteria

• {"criterion_text":"- Written informed consent must be obtained before any assessment is performed."}
• {"criterion_text":"- Male or female ≥ 18 to ≤ 80 years of age at signing of informed consent."}
• {"criterion_text":"- 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 (3.9 mmol/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. Local laboratory values should be calculated using the Friedewald formula for consistency across study sites if the Screening visit occurs prior to the Baseline CCTA Visit. If the Screening and Baseline Visits occur on the same day, then the LDL-C value will be assessed on the central laboratory sample. If the center can only perform the direct LDL-C test, then the local lab should also obtain the total cholesterol, HDL-C, and triglycerides results so that the LDL-C can be calculated using the Friedewald estimation.."}
• {"criterion_text":"- 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. Local laboratory values should be calculated using the Friedewald formula for consistency across study sites. If the center can only perform the direct LDL-C test, then the local lab should also obtain the total cholesterol, HDL-C, and triglycerides results so that the LDL-C can be calculated using the Friedewald estimation."}
• {"criterion_text":"- Participants having NOCAD without previous cardiovascular events: NOCAD is defined as: 1) Participants with a CT-adapted Leaman score >5 and a diameter stenosis of <50%. OR 2) Participants with a CT-adapted Leaman score >5, a diameter stenosis ≥50%* but with FFRCT ≥0.76**. Notes: *=In case of left main CAD, diameter stenosis is ≥40%. **=In case of FFRCT between ≥0.76 and 0.80, participant eligibility will be assessed and determined by the Imaging Core Lab based on the location of the lesion, proximality of the lesion, delta FFRCT and diffuseness of coronary artery disease, (Cury et al 2022). FFRCT and CT-adapted Leaman score will be determined by the Imaging Core Lab. 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 as described above and as assessed by the Imaging Core Lab."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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 Baseline Visit."}

Exclusion criteria

• {"criterion_text":"- Previous myocardial infarction (MI), or prior coronary revascularization [percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG)]."}
• {"criterion_text":"- Planned revascularization (PCI or CABG)."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Pacemaker or implantable cardioverter-defibrillator (ICD) in situ."}
• {"criterion_text":"- Systolic Left Ventricle Ejection Fraction <30% at the Screening Visit."}
• {"criterion_text":"- Uncontrolled severe hypertension: mean systolic blood pressure >180 mmHg or mean diastolic blood pressure >110 mmHg prior to randomization (assessed at the Screening Visit) despite antihypertensive therapy."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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 aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3x upper limit of normal (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."}
• {"criterion_text":"- Local creatine kinase (CK) values of either, unless a more stringent threshold is mandated by a local regulatory authority (e.g., ≥3x ULN in Korea according to MFDS internal guideline): • CK values ≥5x ULN at the Screening Visit for participants on maximally tolerated statin therapy or who are statin intolerant. • CK values ≥5x ULN at Screening and before entering the Statin Optimization Period and confirmed by repeat test within 7 days at Screening or based on Investigator’s judgement for participants entering the Statin Optimization Period (who will be switched to or initiated on the protocol-specified dose of high-intensity statin of atorvastatin ≥40 mg QD or rosuvastatin ≥20 mg QD during the Statin Optimization Period)."}
• {"criterion_text":"- Local CK values ≥5x ULN at the Statin Optimization 3 Visit unless a more stringent threshold is mandated by a local regulatory authority (e.g., ≥3x ULN in Korea according to MFDS internal guideline) and monitored according to national guidelines and statin label during the Statin Optimization Period"}
• {"criterion_text":"- Participant with myopathy at the Statin Optimization 3 Visit."}
• {"criterion_text":"- Heart failure New York Heart Association (NYHA) class III or class IV at the Screening Visit."}

Primary endpoints

• {"endpoint_text":"- Percentage change from baseline to Month 24 in total coronary atheroma volume","definition_or_measurement_approach":"Total coronary atheroma volume assessed by coronary computed tomography angiography (CCTA) from baseline to Month 24."}

Secondary endpoints

• {"endpoint_text":"- Percentage change in LDL-C from baseline to Month 24","definition_or_measurement_approach":"Percentage change in LDL-C measured from baseline to Month 24 (LDL-C assessed using local lab at screening and central laboratory at baseline and per protocol)."}
• {"endpoint_text":"- Percentage change in low attenuation plaque volume evaluated by CCTA","definition_or_measurement_approach":"Low attenuation plaque volume assessed by CCTA; percentage change from baseline measured by Imaging Core Lab."}
• {"endpoint_text":"- Percentage of participants with progression, regression, or no change of total plaque atheroma","definition_or_measurement_approach":"Proportion of participants classified as progression, regression, or no change of total plaque atheroma volume; definitions to be specified in the statistical analysis plan (SAP) and determined by the Imaging Core Lab."}
• {"endpoint_text":"- incidence, severity, and relationship to study drug of TEAEs and Serious Adverse Events (SAEs)","definition_or_measurement_approach":"Safety endpoints capturing incidence, severity and investigator assessment of relationship to study drug of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)."}

Italy

Latest Decision Or Authorization Date

09-05-2025

Number Of Sites

4

Number Of Participants

25

France

Latest Decision Or Authorization Date

09-05-2025

Number Of Sites

5

Number Of Participants

25

Spain

Latest Decision Or Authorization Date

08-05-2025

Number Of Sites

9

Number Of Participants

34

Ireland

Latest Decision Or Authorization Date

11-09-2025

Number Of Sites

2

Number Of Participants

50

Belgium

Latest Decision Or Authorization Date

25-09-2025

Number Of Sites

5

Number Of Participants

27

Hungary

Latest Decision Or Authorization Date

15-05-2026

Number Of Sites

2

Number Of Participants

12

Primary sponsor

Full Name

Novartis Pharma AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

Parexel International (IRL) Limited

Name

Syneos Health Inc.

Name

IQVIA Limited

Name

Medpace Reference Laboratories LLC

Name

Perceptive Informatics Inc.

Responsibilities

Imaging

Third parties

• {"country":"Italy","full_name":"Phardis S.r.l.","duties_or_roles":"Local equipment storage","organisation_type":"Pharmaceutical company"}
• {"country":"Hungary","full_name":"UPS Healthcare Hungary Zrt.","duties_or_roles":"Re-labeling of locally purchased drugs","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"DATAMAP-Gesellschaft fuer Datenmanagement Datenanalyse und Datenpraesentation mbH","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Medpace Reference Laboratories LLC","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Italy","full_name":"Opis S.r.l.","duties_or_roles":"TMF archive","organisation_type":"Pharmaceutical company"}
• {"country":"Hungary","full_name":"Opt-X-Pense Kft.","duties_or_roles":"Patient compensation","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"Imaging","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Mipharm S.p.A.","duties_or_roles":"Local equipment storage","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}