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

NCT ID: NCT05360446

Last Updated: 2025-12-09

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 610 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-07-08
• Study Completion Date: 2026-10-26

Brief 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.

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).

Conditions

Coronary Artery Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Placebo

Subcutaneous injection

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Subcutaneously administered on Day 1, Month 3 (Day 90), and every 6 months thereafter.

Inclisiran sodium

Subcutaneous injection

Group Type: EXPERIMENTAL

Inclisiran sodium 300 mg

Intervention Type: DRUG

Subcutaneously administered on Days 1, Month 3 (Day 90), and every 6 months thereafter.

Interventions

Inclisiran sodium 300 mg

Subcutaneously administered on Days 1, Month 3 (Day 90), and every 6 months thereafter.

Intervention Type: DRUG

Placebo

Subcutaneously administered on Day 1, Month 3 (Day 90), and every 6 months thereafter.

Intervention Type: DRUG

Eligibility Criteria

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.

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Heart Center Research Llc

Huntsville, Alabama, United States

Alaska Heart and Vascular

Anchorage, Alaska, United States

Cardiovascular Res Found

Beverly Hills, California, United States

UC San Diego Health

La Jolla, California, United States

Stanford Health Care

Stanford, California, United States

Lundquist Inst BioMed at Harbor

Torrance, California, United States

Bridgeport Hospital

Bridgeport, Connecticut, United States

George Washington Univ Medical Ctr

Washington D.C., District of Columbia, United States

Inpatient Research Clinical LLC

Miami Lakes, Florida, United States

NorthShore University Health System

Evanston, Illinois, United States

Reid Physician Associates

Richmond, Indiana, United States

Midwest Heart and Vascular Spec

Overland Park, Kansas, United States

Anderson Medical Research

Ft. Washington, Maryland, United States

Minneapolis Heart Institute

Minneapolis, Minnesota, United States

R Ins For Heart And Vascular Health

Reno, Nevada, United States

Cardio Metabolic Institute

Somerset, New Jersey, United States

Icahn School of Med at Mt Sinai

New York, New York, United States

State Uni of NY at Stony Brook

Stony Brook, New York, United States

Westchester Medical Center

Valhalla, New York, United States

Aultman Hospital

Canton, Ohio, United States

Oregon Health Sciences University

Portland, Oregon, United States

Soltero Cardiovascular Research Center

Dallas, Texas, United States

Orion Medical

Houston, Texas, United States

Inova Fairfax Hospital

Falls Church, Virginia, United States

Virginia Heart

Falls Church, Virginia, United States

Swedish Medical Center-Cardiovascular Research

Seattle, Washington, United States

Univ of Washington Medical Center

Seattle, Washington, United States

Novartis Investigative Site

Caba, Buenos Aires, Argentina

Novartis Investigative Site

Buenos Aires, , Argentina

Novartis Investigative Site

Auchenflower, Queensland, Australia

Novartis Investigative Site

Chemside, Queensland, Australia

Novartis Investigative Site

Milton, Queensland, Australia

Novartis Investigative Site

Leabrook, South Australia, Australia

Novartis Investigative Site

Turnhout, Antwerpen, Belgium

Novartis Investigative Site

Genk, Limburg, Belgium

Novartis Investigative Site

Hasselt, Limburg, Belgium

Novartis Investigative Site

Yvoir, Namur, Belgium

Novartis Investigative Site

Aalst, Oost Vlaanderen, Belgium

Novartis Investigative Site

Curitiba, Paraná, Brazil

Novartis Investigative Site

Porto Alegre, Rio Grande do Sul, Brazil

Novartis Investigative Site

São Paulo, , Brazil

Novartis Investigative Site

North York, Ontario, Canada

Novartis Investigative Site

Ottawa, Ontario, Canada

Novartis Investigative Site

Montreal, Quebec, Canada

Novartis Investigative Site

Santiago, Santiago Metropolitan, Chile

Novartis Investigative Site

Beijing, Beijing Municipality, China

Novartis Investigative Site

Nanjing, Jiangsu, China

Novartis Investigative Site

Beijing, , China

Novartis Investigative Site

Shanghai, , China

Novartis Investigative Site

Paris, , France

Novartis Investigative Site

Pessac, , France

Novartis Investigative Site

Poitiers, , France

Novartis Investigative Site

Toulouse, , France

Novartis Investigative Site

Budapest, , Hungary

Novartis Investigative Site

Szeged, , Hungary

Novartis Investigative Site

Bangalore, Karnataka, India

Novartis Investigative Site

New Delhi, National Capital Territory of Delhi, India

Novartis Investigative Site

New Delhi, National Capital Territory of Delhi, India

Novartis Investigative Site

Chennai, Tamil Nadu, India

Novartis Investigative Site

Coimbatore, Tamil Nadu, India

Novartis Investigative Site

Lucknow, Uttar Pradesh, India

Novartis Investigative Site

Dehradun, Uttarakhand, India

Novartis Investigative Site

New Delhi, , India

Novartis Investigative Site

Dublin, Ireland, Ireland

Novartis Investigative Site

Galway, , Ireland

Novartis Investigative Site

Milan, MI, Italy

Novartis Investigative Site

Milan, MI, Italy

Novartis Investigative Site

Rozzano, MI, Italy

Novartis Investigative Site

Torino, TO, Italy

Novartis Investigative Site

Miyhazaki, Miyazaki, Japan

Novartis Investigative Site

Urasoe, Okinawa, Japan

Novartis Investigative Site

Izumisano, Osaka, Japan

Novartis Investigative Site

Kyoto, , Japan

Novartis Investigative Site

Bundang Gu, Gyeonggi-do, South Korea

Novartis Investigative Site

Goyang-si, Gyeonggi-do, South Korea

Novartis Investigative Site

Seoul, , South Korea

Novartis Investigative Site

Seoul, , South Korea

Novartis Investigative Site

Barcelona, Catalonia, Spain

Novartis Investigative Site

A Coruña, , Spain

Novartis Investigative Site

Barcelona, , Spain

Novartis Investigative Site

Córdoba, , Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Salamanca, , Spain

Novartis Investigative Site

Valencia, , Spain

Novartis Investigative Site

Geneva, , Switzerland

Novartis Investigative Site

Lugano, , Switzerland

Novartis Investigative Site

Newcastle upon Tyne, Tyne and Wear, United Kingdom

Novartis Investigative Site

Edinburgh, , United Kingdom

Countries

United States; Argentina; Australia; Belgium; Brazil; Canada; Chile; China; France; Hungary; India; Ireland; Italy; Japan; South Korea; Spain; Switzerland; United Kingdom

References

Revaiah PC, Serruys PW, Onuma Y, Andreini D, Budoff MJ, Sharif F, Chernofsky A, Vikarunnessa S, Wiethoff AJ, Yates D, Achouba A. Design and rationale of a randomized clinical trial assessing the effect of inclisiran on atherosclerotic plaque in individuals without previous cardiovascular event and without flow- limiting lesions identified in an in-hospital screening: The VICTORION-PLAQUE primary prevention trial. Am Heart J. 2026 Jan;291:199-212. doi: 10.1016/j.ahj.2025.08.001. Epub 2025 Aug 30.

Reference Type: DERIVED

PMID: 40769373 (View on PubMed)

Other Identifiers

2021-004601-47

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CKJX839D12303

Identifier Type: -

Identifier Source: org_study_id