Clinical trial NCT05360446: 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
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Coronary Artery Disease
Keywords: Inclisiran
KJX839
Atherosclerotic plaques
CCTA
CT-adapted Leaman score
LDL-C
FFRct
NOCAD
PCSK9 inhibitor
TAV
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2022-05-04
Enrollment: 608
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multi-center, randomized, double-blind, placebo-controlled, parallel-group
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Percentage change in total coronary atheroma volume
timeFrame: From baseline to month 24
Secondary outcomes:
measure: Percentage change in LDL-C
timeFrame: From baseline to month 24
measure: Percentage change in low attenuation plaque volume evaluated by CCTA
timeFrame: From baseline to month 24
measure: Percentage of participants with progression, regression, or no change of total plaque atheroma volume
timeFrame: From baseline to month 24
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Heart Center Research Llc
state: Alabama
city: Anchorage
country: United States
facility: Alaska Heart and Vascular
state: Alaska
city: Beverly Hills
country: United States
facility: Cardiovascular Res Found
state: California
city: La Jolla
country: United States
facility: UC San Diego Health
state: California
city: Stanford
country: United States
facility: Stanford Health Care
state: California
city: Torrance
country: United States
facility: Lundquist Inst BioMed at Harbor
state: California
city: Bridgeport
country: United States
facility: Bridgeport Hospital
state: Connecticut
city: Washington
country: United States
facility: George Washington Univ Medical Ctr
state: District of Columbia
city: Miami Lakes
country: United States
facility: Inpatient Research Clinical LLC
state: Florida
city: Miami
country: United States
facility: MCVI Baptist Hlth of S FL
state: Florida
city: Evanston
country: United States
facility: NorthShore University Health System
state: Illinois
city: Richmond
country: United States
facility: Reid Physician Associates
state: Indiana
city: Overland Park
country: United States
facility: Midwest Heart and Vascular Spec
state: Kansas
city: Fort Washington
country: United States
facility: Anderson Medical Research
state: Maryland
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute
state: Minnesota
city: Reno
country: United States
facility: R Ins For Heart And Vascular Health
state: Nevada
city: Somerset
country: United States
facility: Cardio Metabolic Institute
state: New Jersey
city: New York
country: United States
facility: Icahn School of Med at Mt Sinai
state: New York
city: Stony Brook
country: United States
facility: State Uni of NY at Stony Brook
state: New York
city: Valhalla
country: United States
facility: Westchester Medical Center
state: New York
city: Canton
country: United States
facility: Aultman Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Dallas
country: United States
facility: Soltero Cardiovascular Research Center
state: Texas
city: Houston
country: United States
facility: Orion Medical
state: Texas
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Falls Church
country: United States
facility: Virginia Heart
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center-Cardiovascular Research
state: Washington
city: Seattle
country: United States
facility: Univ of Washington Medical Center
state: Washington
city: Ciudad Autonoma de Bs As
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Auchenflower
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Chemside
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Milton
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Leabrook
country: Australia
facility: Novartis Investigative Site
state: South Australia
city: Aalst
country: Belgium
facility: Novartis Investigative Site
city: Genk
country: Belgium
facility: Novartis Investigative Site
city: Hasselt
country: Belgium
facility: Novartis Investigative Site
city: Turnhout
country: Belgium
facility: Novartis Investigative Site
city: Yvoir
country: Belgium
facility: Novartis Investigative Site
city: Curitiba
country: Brazil
facility: Novartis Investigative Site
state: PR
city: Porto Alegre
country: Brazil
facility: Novartis Investigative Site
state: RS
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
city: North York
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Ottawa
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Santiago
country: Chile
facility: Novartis Investigative Site
state: RM
city: Nanjing
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Beijing
country: China
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Pessac
country: France
facility: Novartis Investigative Site
city: Poitiers
country: France
facility: Novartis Investigative Site
city: Toulouse 4
country: France
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Szeged
country: Hungary
facility: Novartis Investigative Site
city: New Delhi
country: India
facility: Novartis Investigative Site
state: Delhi
city: New Delhi
country: India
facility: Novartis Investigative Site
state: Delhi
city: Bangalore
country: India
facility: Novartis Investigative Site
state: Karnataka
city: Chennai
country: India
facility: Novartis Investigative Site
state: Tamil Nadu
city: Lucknow
country: India
facility: Novartis Investigative Site
state: Uttar Pradesh
city: Dehradun
country: India
facility: Novartis Investigative Site
state: Uttarakhand
city: Coimbatore
country: India
facility: Novartis Investigative Site
city: New Delhi
country: India
facility: Novartis Investigative Site
city: Dublin
country: Ireland
facility: Novartis Investigative Site
city: Galway
country: Ireland
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Rozzano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Torino
country: Italy
facility: Novartis Investigative Site
state: TO
city: Miyhazaki-city
country: Japan
facility: Novartis Investigative Site
state: Miyazaki
city: Urasoe
country: Japan
facility: Novartis Investigative Site
state: Okinawa
city: Izumisano-city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Kyoto
country: Japan
facility: Novartis Investigative Site
city: Bundang Gu
country: Korea, Republic of
facility: Novartis Investigative Site
state: Gyeonggi Do
city: Goyang si
country: Korea, Republic of
facility: Novartis Investigative Site
state: Gyeonggi Do
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Cordoba
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Salamanca
country: Spain
facility: Novartis Investigative Site
state: Castilla Y Leon
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: A Coruna
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Geneve 14
country: Switzerland
facility: Novartis Investigative Site
city: Lugano
country: Switzerland
facility: Novartis Investigative Site
city: Edinburgh
country: United Kingdom
facility: Novartis Investigative Site
city: Newcastle upon Tyne
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: