Coronary Computed Tomography Study to Assess the Effect of Inclisiran in Addition to Maximally Tolerated Statin Therapy on Atherosclerotic Plaque Progression in Participants With a Diagnosis of Non-obstructive Coronary Artery Disease Without Previous Cardiovascular Events
Purpose
CKJX839D12303 is a research study to determine if the study treatment, called inclisiran, in comparison to placebo taken in addition to statin medication can effectively reduce the total amount of plaque formed in the heart's vessels as measured by coronary computed tomography angiography (CCTA) from baseline to month 24. This study is being conducted in eligible participants with a diagnosis of non-obstructive coronary artery disease (NOCAD), where the coronary arteries are blocked less than 50%, and with no previous cardiovascular events.
Condition
- Coronary Artery Disease
Eligibility
- Eligible Ages
- Between 18 Years and 80 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- 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:. 1. Participant with CT-adapted Leaman score >5. and a diameter stenosis <50% or 2. Participants with a CT-adapted Leaman score >5, a diameter stenosis ≥50% but with FFRCT ≥0.76. - 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. - 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.
Exclusion Criteria
- 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.
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- Multi-center, randomized, double-blind, placebo-controlled, parallel-group
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
- Masking Description
- Sponsor personnel participating in the study conducted will be blinded also.
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Placebo Comparator Placebo |
Subcutaneous injection |
|
|
Experimental Inclisiran sodium |
Subcutaneous injection |
|
Recruiting Locations
Washington Hospital Center Medstar
Washington, District of Columbia 20010
Washington, District of Columbia 20010
More Details
- Status
- Recruiting
- Sponsor
- Novartis Pharmaceuticals
Detailed Description
The purpose of this study is to evaluate the efficacy of inclisiran compared to placebo on top of maximally tolerated dose of statin therapy in reducing total coronary atheroma volume assessed by CCTA in participants with a diagnosis of Non-Obstructive Coronary Artery Disease (NOCAD) without previous cardiovascular events, who have an LDL-C ≥55 mg/dL (1.4 mmol//L), no significant pressure drop in Fractional Flow Reserve Computed Tomography (FFRCT) and a CT-adapted Leaman score >5 despite the use of maximally tolerated statin therapy(and if applicable, another LLT on top of statin therapy for at least 30 days in up to 20% of randomized participants).