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 (V-PLAQUE)

A Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel-group Phase IIIb Study Evaluating the Effect of Inclisiran on Atherosclerotic Plaque Progression Assessed by Coronary Computed Tomography Angiography (CCTA) in Participants With a Diagnosis of Non-obstructive Coronary Artery Disease Without Previous Cardiovascular Events (VICTORION-PLAQUE)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: Placebo; Drug: Inclisiran sodium 300 mg

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).

• Study Type: Interventional
• Enrollment (Actual): 610
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1428DCO
    • Novartis Investigative Site
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1119ACN
      • Novartis Investigative Site
• Australia
  • Queensland
    • Auchenflower, Queensland, Australia, 4066
      • Novartis Investigative Site
    • Chemside, Queensland, Australia, 4032
      • Novartis Investigative Site
    • Milton, Queensland, Australia, 4064
      • Novartis Investigative Site
  • South Australia
    • Leabrook, South Australia, Australia, 5068
      • Novartis Investigative Site
• Belgium
  • Antwerpen
    • Turnhout, Antwerpen, Belgium, 2300
      • Novartis Investigative Site
  • Limburg
    • Genk, Limburg, Belgium, 3600
      • Novartis Investigative Site
    • Hasselt, Limburg, Belgium, 3500
      • Novartis Investigative Site
  • Namur
    • Yvoir, Namur, Belgium, 5530
      • Novartis Investigative Site
  • Oost Vlaanderen
    • Aalst, Oost Vlaanderen, Belgium, 9300
      • Novartis Investigative Site
• Brazil
  • São Paulo, Brazil, 01409-902
    • Novartis Investigative Site
  • Paraná
    • Curitiba, Paraná, Brazil, 80040-050
      • Novartis Investigative Site
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90560-032
      • Novartis Investigative Site
• Canada
  • Ontario
    • North York, Ontario, Canada, M6B 3H7
      • Novartis Investigative Site
    • Ottawa, Ontario, Canada, K1Y 4W7
      • Novartis Investigative Site
  • Quebec
    • Montreal, Quebec, Canada, H1T 1C8
      • Novartis Investigative Site
• Chile
  • Santiago Metropolitan
    • Santiago, Santiago Metropolitan, Chile, 8380465
      • Novartis Investigative Site
• China
  • Beijing, China, 100050
    • Novartis Investigative Site
  • Shanghai, China, 200080
    • Novartis Investigative Site
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100013
      • Novartis Investigative Site
  • Jiangsu
    • Nanjing, Jiangsu, China, 211166
      • Novartis Investigative Site
• France
  • Paris, France, 75013
    • Novartis Investigative Site
  • Pessac, France, 33604
    • Novartis Investigative Site
  • Poitiers, France, 86021
    • Novartis Investigative Site
  • Toulouse, France, 31054
    • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, H-1083
    • Novartis Investigative Site
  • Szeged, Hungary, 6725
    • Novartis Investigative Site
• India
  • New Delhi, India, 110025
    • Novartis Investigative Site
  • Karnataka
    • Bangalore, Karnataka, India, 560069
      • Novartis Investigative Site
  • National Capital Territory of Delhi
    • New Delhi, National Capital Territory of Delhi, India, 110060
      • Novartis Investigative Site
    • New Delhi, National Capital Territory of Delhi, India, 110017
      • Novartis Investigative Site
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600006
      • Novartis Investigative Site
    • Coimbatore, Tamil Nadu, India, 641009
      • Novartis Investigative Site
  • Uttar Pradesh
    • Lucknow, Uttar Pradesh, India, 226003
      • Novartis Investigative Site
  • Uttarakhand
    • Dehradun, Uttarakhand, India, 248001
      • Novartis Investigative Site
• Ireland
  • Galway, Ireland, H91 YR71
    • Novartis Investigative Site
  • Ireland
    • Dublin, Ireland, Ireland, D03 VX82
      • Novartis Investigative Site
• Italy
  • MI
    • Milan, MI, Italy, 20138
      • Novartis Investigative Site
    • Milan, MI, Italy, 20157
      • Novartis Investigative Site
    • Rozzano, MI, Italy, 20089
      • Novartis Investigative Site
  • TO
    • Torino, TO, Italy, 10126
      • Novartis Investigative Site
• Japan
  • Kyoto, Japan, 6078062
    • Novartis Investigative Site
  • Miyazaki
    • Miyhazaki, Miyazaki, Japan, 8802102
      • Novartis Investigative Site
  • Okinawa
    • Urasoe, Okinawa, Japan, 901-2102
      • Novartis Investigative Site
  • Osaka
    • Izumisano, Osaka, Japan, 5988577
      • Novartis Investigative Site
• South Korea
  • Seoul, South Korea, 03722
    • Novartis Investigative Site
  • Seoul, South Korea, 07804
    • Novartis Investigative Site
  • Gyeonggi-do
    • Bundang Gu, Gyeonggi-do, South Korea, 13620
      • Novartis Investigative Site
    • Goyang-si, Gyeonggi-do, South Korea, 10380
      • Novartis Investigative Site
• Spain
  • A Coruña, Spain, 15006
    • Novartis Investigative Site
  • Barcelona, Spain, 08035
    • Novartis Investigative Site
  • Barcelona, Spain, 08041
    • Novartis Investigative Site
  • Córdoba, Spain, 14004
    • Novartis Investigative Site
  • Madrid, Spain, 28034
    • Novartis Investigative Site
  • Madrid, Spain, 28040
    • Novartis Investigative Site
  • Salamanca, Spain, 37007
    • Novartis Investigative Site
  • Valencia, Spain, 46010
    • Novartis Investigative Site
• Switzerland
  • Geneva, Switzerland, 1211
    • Novartis Investigative Site
  • Lugano, Switzerland, 6900
    • Novartis Investigative Site
• United Kingdom
  • Edinburgh, United Kingdom, ED16 4SA
    • Novartis Investigative Site
  • Tyne and Wear
    • Newcastle upon Tyne, Tyne and Wear, United Kingdom, NE7 7DN
      • Novartis Investigative Site
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Heart Center Research LLC
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Alaska Heart and Vascular
  • California
    • Beverly Hills, California, United States, 90210
      • Cardiovascular Res Found
    • La Jolla, California, United States, 92037
      • UC San Diego Health
    • Stanford, California, United States, 94305
      • Stanford Health Care
    • Torrance, California, United States, 90509-2910
      • Lundquist Inst BioMed at Harbor
  • Connecticut
    • Bridgeport, Connecticut, United States, 06610
      • Bridgeport Hospital
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20037
      • George Washington Univ Medical Ctr
  • Florida
    • Miami Lakes, Florida, United States, 33014
      • Inpatient Research Clinical LLC
  • Illinois
    • Evanston, Illinois, United States, 60201
      • NorthShore University Health System
  • Indiana
    • Richmond, Indiana, United States, 47374
      • Reid Physician Associates
  • Kansas
    • Overland Park, Kansas, United States, 66211
      • Midwest Heart and Vascular Spec
  • Maryland
    • Ft. Washington, Maryland, United States, 20744
      • Anderson Medical Research
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Minneapolis Heart Institute
  • Nevada
    • Reno, Nevada, United States, 89502
      • R Ins For Heart And Vascular Health
  • New Jersey
    • Somerset, New Jersey, United States, 08873
      • Cardio Metabolic Institute
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Med at Mt Sinai
    • Stony Brook, New York, United States, 11794-3362
      • State Uni of NY at Stony Brook
    • Valhalla, New York, United States, 10595
      • Westchester Medical Center
  • Ohio
    • Canton, Ohio, United States, 44710
      • Aultman Hospital
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health Sciences University
  • Texas
    • Dallas, Texas, United States, 75226
      • Soltero Cardiovascular Research Center
    • Houston, Texas, United States, 77034
      • Orion Medical
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax Hospital
    • Falls Church, Virginia, United States, 22042
      • Virginia Heart
  • Washington
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center-Cardiovascular Research
    • Seattle, Washington, United States, 98195
      • Univ of Washington Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Subcutaneous injection	Drug: Placebo; Subcutaneously administered on Day 1, Month 3 (Day 90), and every 6 months thereafter.
Experimental: Inclisiran sodium; Subcutaneous injection	Drug: Inclisiran sodium 300 mg; Subcutaneously administered on Days 1, Month 3 (Day 90), and every 6 months thereafter.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage change in LDL-C	Full fasting lipid panel will be collected throughout the study beginning at baseline.	From baseline to month 24
Percentage change in low attenuation plaque volume evaluated by CCTA	Evaluating inclisiran compared to placebo in 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	Evaluating inclisiran compared to placebo in percentage of participants experiencing progression, regression, or no change of total atheroma volume.	From baseline to month 24

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 8, 2022
• Primary Completion (Estimated): October 26, 2026
• Study Completion (Estimated): October 26, 2026

Study Registration Dates

• First Submitted: April 29, 2022
• First Submitted That Met QC Criteria: April 29, 2022
• First Posted (Actual): May 4, 2022

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Inclisiran; LDL-C; FFRct; PCSK9 inhibitor; CCTA; KJX839; Atherosclerotic plaques; CT-adapted Leaman score; NOCAD; TAV
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Myocardial Ischemia; Pathological Conditions, Signs and Symptoms; Coronary Artery Disease; Plaque, Atherosclerotic
• Other Study ID Numbers: CKJX839D12303; 2021-004601-47 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No