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

NCT05360446 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: CKJX839D123032021-004601-47
• Study Type: interventional
• Target: 610
• Locations: 18 countries
• Sites: 89

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.

Conditions

Coronary Artery Disease

Keywords

Inclisiran; KJX839; Atherosclerotic plaques; CCTA; CT-adapted Leaman score; LDL-C; FFRct; NOCAD; PCSK9 inhibitor; TAV

Outcome Measures

Primary Outcomes (1)

• Percentage change in total coronary atheroma volume

  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.

  From baseline to month 24

Secondary Outcomes (3)

• Percentage change in LDL-C

  From baseline to month 24

• Percentage change in low attenuation plaque volume evaluated by CCTA

  From baseline to month 24

• Percentage of participants with progression, regression, or no change of total plaque atheroma volume

  From baseline to month 24

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Subcutaneous injection

Drug: Placebo

Inclisiran sodium

EXPERIMENTAL

Subcutaneous injection

Drug: Inclisiran sodium 300 mg

Interventions

Placebo DRUG

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

Placebo

Inclisiran sodium 300 mg DRUG

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

Inclisiran sodium

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:.
• Participant with CT-adapted Leaman score \>5. and a diameter stenosis \<50% or
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (89)

Heart Center Research Llc

Huntsville, Alabama, 35801, United States

Location

Alaska Heart and Vascular

Anchorage, Alaska, 99508, United States

Location

Cardiovascular Res Found

Beverly Hills, California, 90210, United States

Location

UC San Diego Health

La Jolla, California, 92037, United States

Location

Stanford Health Care

Stanford, California, 94305, United States

Location

Lundquist Inst BioMed at Harbor

Torrance, California, 90509-2910, United States

Location

Bridgeport Hospital

Bridgeport, Connecticut, 06610, United States

Location

George Washington Univ Medical Ctr

Washington D.C., District of Columbia, 20037, United States

Location

Inpatient Research Clinical LLC

Miami Lakes, Florida, 33014, United States

Location

NorthShore University Health System

Evanston, Illinois, 60201, United States

Location

Reid Physician Associates

Richmond, Indiana, 47374, United States

Location

Midwest Heart and Vascular Spec

Overland Park, Kansas, 66211, United States

Location

Anderson Medical Research

Ft. Washington, Maryland, 20744, United States

Location

Minneapolis Heart Institute

Minneapolis, Minnesota, 55407, United States

Location

R Ins For Heart And Vascular Health

Reno, Nevada, 89502, United States

Location

Cardio Metabolic Institute

Somerset, New Jersey, 08873, United States

Location

Icahn School of Med at Mt Sinai

New York, New York, 10029, United States

Location

State Uni of NY at Stony Brook

Stony Brook, New York, 11794-3362, United States

Location

Westchester Medical Center

Valhalla, New York, 10595, United States

Location

Aultman Hospital

Canton, Ohio, 44710, United States

Location

Oregon Health Sciences University

Portland, Oregon, 97239, United States

Location

Soltero Cardiovascular Research Center

Dallas, Texas, 75226, United States

Location

Orion Medical

Houston, Texas, 77034, United States

Location

Inova Fairfax Hospital

Falls Church, Virginia, 22042, United States

Location

Virginia Heart

Falls Church, Virginia, 22042, United States

Location

Swedish Medical Center-Cardiovascular Research

Seattle, Washington, 98122, United States

Location

Univ of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Novartis Investigative Site

Caba, Buenos Aires, C1119ACN, Argentina

Location

Novartis Investigative Site

Buenos Aires, C1428DCO, Argentina

Location

Novartis Investigative Site

Auchenflower, Queensland, 4066, Australia

Location

Novartis Investigative Site

Chemside, Queensland, 4032, Australia

Location

Novartis Investigative Site

Milton, Queensland, 4064, Australia

Location

Novartis Investigative Site

Leabrook, South Australia, 5068, Australia

Location

Novartis Investigative Site

Turnhout, Antwerpen, 2300, Belgium

Location

Novartis Investigative Site

Genk, Limburg, 3600, Belgium

Location

Novartis Investigative Site

Hasselt, Limburg, 3500, Belgium

Location

Novartis Investigative Site

Yvoir, Namur, 5530, Belgium

Location

Novartis Investigative Site

Aalst, Oost Vlaanderen, 9300, Belgium

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Novartis Investigative Site

Curitiba, Paraná, 80040-050, Brazil

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Novartis Investigative Site

Porto Alegre, Rio Grande do Sul, 90560-032, Brazil

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Novartis Investigative Site

São Paulo, 01409-902, Brazil

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Novartis Investigative Site

North York, Ontario, M6B 3H7, Canada

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Novartis Investigative Site

Ottawa, Ontario, K1Y 4W7, Canada

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Novartis Investigative Site

Montreal, Quebec, H1T 1C8, Canada

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Novartis Investigative Site

Santiago, Santiago Metropolitan, 8380465, Chile

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Novartis Investigative Site

Beijing, Beijing Municipality, 100013, China

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Novartis Investigative Site

Nanjing, Jiangsu, 211166, China

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Novartis Investigative Site

Beijing, 100050, China

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Novartis Investigative Site

Shanghai, 200080, China

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Novartis Investigative Site

Paris, 75013, France

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Novartis Investigative Site

Pessac, 33604, France

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Novartis Investigative Site

Poitiers, 86021, France

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Novartis Investigative Site

Toulouse, 31054, France

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Novartis Investigative Site

Budapest, H-1083, Hungary

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Novartis Investigative Site

Szeged, 6725, Hungary

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Novartis Investigative Site

Bangalore, Karnataka, 560069, India

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Novartis Investigative Site

New Delhi, National Capital Territory of Delhi, 110017, India

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Novartis Investigative Site

New Delhi, National Capital Territory of Delhi, 110060, India

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Novartis Investigative Site

Chennai, Tamil Nadu, 600006, India

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Novartis Investigative Site

Coimbatore, Tamil Nadu, 641009, India

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Novartis Investigative Site

Lucknow, Uttar Pradesh, 226003, India

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Novartis Investigative Site

Dehradun, Uttarakhand, 248001, India

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Novartis Investigative Site

New Delhi, 110025, India

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Novartis Investigative Site

Dublin, Ireland, D03 VX82, Ireland

Location

Novartis Investigative Site

Galway, H91 YR71, Ireland

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Novartis Investigative Site

Milan, MI, 20138, Italy

Location

Novartis Investigative Site

Milan, MI, 20157, Italy

Location

Novartis Investigative Site

Rozzano, MI, 20089, Italy

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Novartis Investigative Site

Torino, TO, 10126, Italy

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Novartis Investigative Site

Miyhazaki, Miyazaki, 8802102, Japan

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Novartis Investigative Site

Urasoe, Okinawa, 901-2102, Japan

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Novartis Investigative Site

Izumisano, Osaka, 5988577, Japan

Location

Novartis Investigative Site

Kyoto, 6078062, Japan

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Novartis Investigative Site

Bundang Gu, Gyeonggi-do, 13620, South Korea

Location

Novartis Investigative Site

Goyang-si, Gyeonggi-do, 10380, South Korea

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Novartis Investigative Site

Seoul, 03722, South Korea

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Novartis Investigative Site

Seoul, 07804, South Korea

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Novartis Investigative Site

A Coruña, 15006, Spain

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Novartis Investigative Site

Barcelona, 08035, Spain

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Novartis Investigative Site

Barcelona, 08041, Spain

Location

Novartis Investigative Site

Córdoba, 14004, Spain

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Novartis Investigative Site

Madrid, 28034, Spain

Location

Novartis Investigative Site

Madrid, 28040, Spain

Location

Novartis Investigative Site

Salamanca, 37007, Spain

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Novartis Investigative Site

Valencia, 46010, Spain

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Novartis Investigative Site

Geneva, 1211, Switzerland

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Novartis Investigative Site

Lugano, 6900, Switzerland

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Novartis Investigative Site

Newcastle upon Tyne, Tyne and Wear, NE7 7DN, United Kingdom

Location

Novartis Investigative Site

Edinburgh, ED16 4SA, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 40769373 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease; Plaque, Atherosclerotic

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Sponsor personnel participating in the study conducted will be blinded also.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Multi-center, randomized, double-blind, placebo-controlled, parallel-group

Study Record Dates

• First Submitted: April 29, 2022
• First Posted: May 4, 2022
• Study Start: July 8, 2022
• Primary Completion (Estimated): October 26, 2026
• Study Completion (Estimated): October 26, 2026
• Last Updated: April 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (27); AR (2); FR (4); CA (3); BR (3); IN (8); GB (2); IT (4); BE (5); HU (2); KR (4); CH (2); CN (4); CL (1); ES (8); IE (2); AU (4); JP (4)