Last Update: Oct 01, 2024
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)
ClinicalTrials.gov Identifier:
Novartis Reference Number:CKJX839D12303
All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation.

Study Description

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. 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).

Coronary Artery Disease
Phase3
Recruiting
600
Jul 08, 2022
Jan 25, 2027
All
18 Years - 80 Years (Adult, Older Adult)

Interventions

Drug

Inclisiran sodium 300 mg

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

Placebo

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

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.
* 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.

Novartis Investigative Site

Recruiting

Ciudad Autonoma de Bs As,Buenos Aires,C1119acn,Argentina

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Buenos Aires,C1428dco,Argentina

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Auchenflower,Queensland,4066,Australia

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Chemside,Queensland,4032,Australia

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Milton,Queensland,4064,Australia

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Leabrook,South Australia,5068,Australia

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Genk,3600,Belgium

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Hasselt,3500,Belgium

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Turnhout,2300,Belgium

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Yvoir,5530,Belgium

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Aalst,9300,Belgium

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Curitiba,PR,80040-050,Brazil

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Porto Alegre,RS,90560 030,Brazil

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Sao Paulo,01409-902,Brazil

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North York,Ontario,M6b 3h7,Canada

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Montreal,Quebec,H1t 1c8,Canada

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Temuco,Region De La Araucania,4781156,Chile

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Santiago,RM,8380465,Chile

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Beijing,100029,China

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Beijing,100050,China

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Pessac Cedex,33604,France

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Toulouse 4,31054,France

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Budapest,H-1083,Hungary

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Szeged,6720,Hungary

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Bangalore,Karnataka,560 069,India

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Chennai,Tamil Nadu,600006,India

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Lucknow,Uttar Pradesh,226003,India

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Dehradun,Uttarakhand,248001,India

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Coimbatore,641 009,India

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New Delhi,Delhi,110 017,India

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New Delhi,110025,India

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New Delhi,Delhi,110 060,India

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Galway,H91 yr71,Ireland

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Dublin,D03 vx82,Ireland

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Milano,MI,20138,Italy

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Torino,TO,10126,Italy

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Kumamoto,860-8556,Japan

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Seoul,03722,Korea, Republic of

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Seoul,07804,Korea, Republic of

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Bundang Gu,Gyeonggi Do,13620,Korea, Republic of

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Goyang si,Gyeonggi Do,10380,Korea, Republic of

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A Coruna,Galicia,15006,Spain

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Barcelona,08041,Spain

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Cordoba,Andalucia,14004,Spain

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Madrid,28034,Spain

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Salamanca,Castilla Y Leon,37007,Spain

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Madrid,28040,Spain

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Barcelona,Catalunya,08035,Spain

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Valencia,Comunidad Valenciana,46010,Spain

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Valencia,Comunidad Valenciana,46014,Spain

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Geneve 14,1211,Switzerland

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Lugano,6903,Switzerland

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Portadown,Nothern Ireland,Bt63 5qq,United Kingdom

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Bradford,West Yorkshire,Bd9 6rj,United Kingdom

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Edinburgh,Ed16 4sa,United Kingdom

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London,Se5 9rs,United Kingdom

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Newcastle upon Tyne,Ne7 7dn,United Kingdom

Westchester Medical Center .

Recruiting

Valhalla,New York,10595,United States

Hasan Ahmad

Stanford Health Care .

Recruiting

Stanford,California,94305,United States

Kendall Rose Harrington
Koen Nieman

MCVI Baptist Hlth of S FL

Recruiting

Miami,Florida,33173,United States

Ruben Dominguez
Jonathan A Fialkow

Heart Center Research Llc .

Recruiting

Huntsville,Alabama,35801,United States

Carolyn Keefer
Michael Ridner

Cardio Metabolic Institute Research

Recruiting

Somerset,New Jersey,08873,United States

Dinesh Singal
Ashley Hansen

Orion Medical

Recruiting

Houston,Texas,77034,United States

Karan Bhalla
Luisa Castelan

Washington Hospital Center Medstar

Recruiting

Washington,District of Columbia,20010,United States

Ron Waksman
Donna Whitman

Anderson Medical Research Main Center

Recruiting

Fort Washington,Maryland,20744,United States

Felton Anderson

Oregon Health Sciences University Main Center

Recruiting

Portland,Oregon,97239,United States

Aynun Naher
Maros Ferencik

NorthShore University Health System Endeavor Health Glenbrook Hosp

Recruiting

Evanston,Illinois,60201,United States

Amit Pursnani
Caitlin Nagy

Icahn School of Med at Mt Sinai .

Recruiting

New York,New York,10029,United States

Jay Krishna Katragadda
Robert Rosenson

George Washington Univ Medical Ctr

Recruiting

Washington,District of Columbia,20037,United States

Andrew Choi
Priscilla Muhanji

Minneapolis Heart Institute

Recruiting

Minneapolis,Minnesota,55407,United States

Haley Hanson
Jonathan Urbach

Lundquist Inst BioMed at Harbor UCLA Medical Center

Recruiting

Torrance,California,90509-2910,United States

Khadije Ahmad
Matthew Jay Budoff

Cardiovascular Res Found

Recruiting

Beverly Hills,California,90210,United States

Lana Levi
Ronald P Karlsberg

Swedish Medical Center-Cardiovascular Research .

Recruiting

Seattle,Washington,98122,United States

Elizabeth Borchard
Santanu Biswas

Lankenau Hospital

Recruiting

Wynnewood,Pennsylvania,19096,United States

Erik Kelly
Stephanie Wright

The Uni of Kansas Medical Center

Recruiting

Kansas City,Kansas,66160,United States

Rebecca Johnson
Thomas Rosamond

State Uni of NY at Stony Brook .

Recruiting

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

On Chen
Uzma Usmani

Inpatient Research Clinical LLC

Recruiting

Miami Lakes,Florida,33014,United States

Alexis Gutierrez
Illyanis Marino

R Ins For Heart And Vascular Health .

Recruiting

Reno,Nevada,89502,United States

Thomas Duythuc To
Zena Sanchez

Bridgeport Hospital .

Recruiting

Bridgeport,Connecticut,06610,United States

Adam Schussheim
Brenda Garcia

UC San Diego Health .

Recruiting

La Jolla,California,92037,United States

Marissa Dzotsi
Michael John Wilkinson

Univ of Washington Medical Center .

Recruiting

Seattle,Washington,98195,United States

Kelley Branch
Kevin Palacpac

Soltero Cardiovascular Research Center .

Recruiting

Dallas,Texas,75226,United States

Cara East
Natalia Feliz

Midwest Heart and Vascular Spec .

Recruiting

Overland Park,Kansas,66211,United States

Chelsea Waller
Stephen Bloom

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