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

Coronary Artery Disease Clinical Trial

— V-PLAQUE  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05360446
• Other study ID #: CKJX839D12303
• Secondary ID: 2021-004601-47
• Status: Recruiting
• Phase: Phase 3
• Start date: July 8, 2022
• Est. completion date: January 15, 2027

Study information

• Verified date: April 2024
• Source: Novartis
• Contact: Novartis Pharmaceuticals
• Phone: 1-888-669-6682
• Email: novartis.email[@]novartis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The purpose of this study is to evaluate the efficacy of inclisiran compared to placebo on top of maximally tolerated statin therapy in reducing total coronary atheroma volume assessed by coronary computed tomography angiography from baseline to month 24 in participants with a diagnosis of NOCAD without previous cardiovascular events, a CT-adapted Leaman score >5 and a FFRct >0.8. Participants will either receive inclisiran 300 mg subcutaneously administered on Day 1, Month 3 (Day 90), and every 6 months up until Month 21. The study duration is 24 months. Participants will have a CCTA performed at baseline and at the month 24/end of study visit.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: January 15, 2027
• Est. primary completion date: January 7, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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 if on statin therapy but not on a maximally tolerated statin therapy; ii) =150 mg/dL if statin naive and without documented statin intolerance; or iii) =70 mg/dL if on a stable (=4 weeks) dose of maximally tolerated statin therapy or if statin intolerant.

• Participants may be pre-identified based on a CCTA or an invasive angiography that is performed as part of standard of care within 12 months prior to the participant's Screening Visit demonstrating:

• Presence of coronary artery plaque with visual diameter stenosis <50% or

• Coronary artery plaque with visual artery stenosis >50% but Fractional Flow Reserve (FFR) >0.8 by special wire measurement (CCTA or coronary angiography)

• Fasting LDL-C local lab value =70 mg/dL at the assessment performed during the Statin Optimization Period 3 Visit for participants going through the Statin Optimization Period.

• Participants having Non-Obstructive Coronary Artery (NOCA)* confirmed by CCTA with FFRct >0.8 and CT-adapted Leaman score >5** or coronary artery plaque with visual diameter stenosis >50% but with FFRct >0.8 and CT-adapted Leaman score >5 without previous cardiovascular events.

*=NOCA is defined as the presence of coronary artery plaque with visual diameter stenosis <50%.

**=CT-adapted Leaman score, which includes information on lesion localization, plaque composition, degree of stenosis by CCTA is demonstrated to be an independent long-term predictor of hard cardiac events.

• 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.

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.

• NOCA participant who was prescreened by the Investigator with visual diameter stenosis >50% but FFR <0.8.

• 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. Participants who enter the Statin Optimization Period must have AST and ALT =3x ULN (as defined by local laboratory reference ranges collected at the Screening Visit) and reported by the Statin Optimization Telephone Visit 1 to be allowed to continue in the Statin Optimization Period.

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia
• Plaque, Atherosclerotic

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Ciudad Autonoma de Bs As	Buenos Aires
Australia	Novartis Investigative Site	Auchenflower	Queensland
Australia	Novartis Investigative Site	Chemside	Queensland
Australia	Novartis Investigative Site	Leabrook	South Australia
Australia	Novartis Investigative Site	Milton	Queensland
Australia	Novartis Investigative Site	Murdoch	Western Australia
Belgium	Novartis Investigative Site	Aalst
Belgium	Novartis Investigative Site	Genk
Belgium	Novartis Investigative Site	Hasselt
Belgium	Novartis Investigative Site	Turnhout
Belgium	Novartis Investigative Site	Yvoir
Brazil	Novartis Investigative Site	Curitiba	PR
Brazil	Novartis Investigative Site	Porto Alegre	RS
Brazil	Novartis Investigative Site	Sao Paulo
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	North York	Ontario
Canada	Novartis Investigative Site	Ottawa	Ontario
Chile	Novartis Investigative Site	Santiago	RM
Chile	Novartis Investigative Site	Temuco	Region De La Araucania
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Hangzhou	Zhejiang
China	Novartis Investigative Site	Nanjing	Jiangsu
China	Novartis Investigative Site	Shanghai
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Paris 13
France	Novartis Investigative Site	Pessac Cedex
France	Novartis Investigative Site	Poitiers
France	Novartis Investigative Site	Toulouse 4
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Szeged
India	Novartis Investigative Site	Bangalore	Karnataka
India	Novartis Investigative Site	Chennai	Tamil Nadu
India	Novartis Investigative Site	Coimbatore
India	Novartis Investigative Site	DehraDun	Uttarakhand
India	Novartis Investigative Site	Kolkata	West Bengal
India	Novartis Investigative Site	Lucknow	Uttar Pradesh
India	Novartis Investigative Site	New Delhi
India	Novartis Investigative Site	New Delhi	Delhi
India	Novartis Investigative Site	New Delhi	Delhi
Ireland	Novartis Investigative Site	Dublin
Ireland	Novartis Investigative Site	Galway
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Rozzano	MI
Italy	Novartis Investigative Site	Torino	TO
Japan	Novartis Investigative Site	Izumisano-city	Osaka
Japan	Novartis Investigative Site	Kumamoto City	Kumamoto
Japan	Novartis Investigative Site	Kyoto-city	Kyoto
Japan	Novartis Investigative Site	Miyhazaki-city	Miyazaki
Japan	Novartis Investigative Site	Urasoe	Okinawa
Korea, Republic of	Novartis Investigative Site	Bundang Gu	Gyeonggi Do
Korea, Republic of	Novartis Investigative Site	Goyang si	Gyeonggi Do
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Spain	Novartis Investigative Site	A Coruna	Galicia
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Cordoba	Andalucia
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Salamanca	Castilla Y Leon
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Switzerland	Novartis Investigative Site	Geneve 14
Switzerland	Novartis Investigative Site	Lugano
United Kingdom	Novartis Investigative Site	Bradford	West Yorkshire
United Kingdom	Novartis Investigative Site	Craigavon	Northern Ireland
United Kingdom	Novartis Investigative Site	Edinburgh
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Newcastle upon Tyne
United States	Alaska Heart and Vascular	Anchorage	Alaska
United States	Cardiovascular Res Found	Beverly Hills	California
United States	Bridgeport Hospital .	Bridgeport	Connecticut
United States	Aultman Hospital Main Centre	Canton	Ohio
United States	Soltero Cardiovascular Research Ctr .	Dallas	Texas
United States	NorthShore University Health System .	Evanston	Illinois
United States	Inova Fairfax Hospital .	Falls Church	Virginia
United States	Virginia Heart	Falls Church	Virginia
United States	Anderson Medical Research Main Center	Fort Washington	Maryland
United States	Orion Medical	Houston	Texas
United States	Heart Center Research Llc .	Huntsville	Alabama
United States	The Uni of Kansas Medical Center	Kansas City	Kansas
United States	UC San Diego Health .	La Jolla	California
United States	U of Louisville Rudd Heart and Lung	Louisville	Kentucky
United States	MCVI Baptist Hlth of S FL	Miami	Florida
United States	Minneapolis Heart Institute	Minneapolis	Minnesota
United States	Icahn School of Med at Mt Sinai .	New York	New York
United States	Midwest Heart and Vascular Spec .	Overland Park	Kansas
United States	Oregon Health Sciences University Main Center	Portland	Oregon
United States	R Ins For Heart And Vascular Health .	Reno	Nevada
United States	Reid Physician Associates	Richmond	Indiana
United States	Swedish Medical Ctr Cardiovascular Re .	Seattle	Washington
United States	Univ of Washington Medical Center .	Seattle	Washington
United States	Cardio Metabolic Institute Research	Somerset	New Jersey
United States	Stanford Health Care .	Stanford	California
United States	State Uni of NY at Stony Brook .	Stony Brook	New York
United States	Lundquist Inst BioMed at Harbor UCLA Medical Center	Torrance	California
United States	Westchester Medical Center .	Valhalla	New York
United States	George Washington Univ Medical Ctr	Washington	District of Columbia
United States	Washington Hospital Center Medstar	Washington	District of Columbia
United States	Lankenau Hospital	Wynnewood	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  Chile,  China,  France,  Hungary,  India,  Ireland,  Italy,  Japan,  Korea, Republic of,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Percentage change in LDL-C	Full fasting lipid panel will be collected throughout the study beginning at baseline.	From baseline to month 24
Secondary	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
Secondary	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