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
Inclisiran sodium 300 mg: Subcutaneously administered on Days 1, Month 3 (Day 90), and every 6 months thereafter.
Placebo: Subcutaneously administered on Day 1, Month 3 (Day 90), and every 6 months thereafter.
Study summary
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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
80 Years
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.
Primary outcome measure(s)
Percentage change in total coronary atheroma volume — From baseline to month 24 Evaluating inclisiran compared to placebo both on top of maximally tolerated statin therapy in reducing total coronary atheroma volume assessed by coronary computed tomography angiography (CCTA) in participants with a diagnosis of non-obstructive coronary artery disease (NOCAD) without previous cardiovascular events.
Trial sites (89)
Facility
City
Region
Status
Heart Center Research Llc
Huntsville
Alabama
Alaska Heart and Vascular
Anchorage
Alaska
Cardiovascular Res Found
Beverly Hills
California
UC San Diego Health
La Jolla
California
Stanford Health Care
Stanford
California
Lundquist Inst BioMed at Harbor
Torrance
California
Bridgeport Hospital
Bridgeport
Connecticut
George Washington Univ Medical Ctr
Washington D.C.
District of Columbia
Inpatient Research Clinical LLC
Miami Lakes
Florida
NorthShore University Health System
Evanston
Illinois
Reid Physician Associates
Richmond
Indiana
Midwest Heart and Vascular Spec
Overland Park
Kansas
Anderson Medical Research
Ft. Washington
Maryland
Minneapolis Heart Institute
Minneapolis
Minnesota
R Ins For Heart And Vascular Health
Reno
Nevada
Cardio Metabolic Institute
Somerset
New Jersey
Icahn School of Med at Mt Sinai
New York
New York
State Uni of NY at Stony Brook
Stony Brook
New York
Westchester Medical Center
Valhalla
New York
Aultman Hospital
Canton
Ohio
Oregon Health Sciences University
Portland
Oregon
Soltero Cardiovascular Research Center
Dallas
Texas
Orion Medical
Houston
Texas
Inova Fairfax Hospital
Falls Church
Virginia
Virginia Heart
Falls Church
Virginia
Swedish Medical Center-Cardiovascular Research
Seattle
Washington
Univ of Washington Medical Center
Seattle
Washington
Novartis Investigative Site
Caba
Buenos Aires
Novartis Investigative Site
Buenos Aires
Argentina
Novartis Investigative Site
Auchenflower
Queensland
Novartis Investigative Site
Chemside
Queensland
Novartis Investigative Site
Milton
Queensland
Novartis Investigative Site
Leabrook
South Australia
Novartis Investigative Site
Turnhout
Antwerpen
Novartis Investigative Site
Genk
Limburg
Novartis Investigative Site
Hasselt
Limburg
Novartis Investigative Site
Yvoir
Namur
Novartis Investigative Site
Aalst
Oost Vlaanderen
Novartis Investigative Site
Curitiba
Paraná
Novartis Investigative Site
Porto Alegre
Rio Grande do Sul
+ 49 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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