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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)

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ClinicalTrials.gov Identifier: NCT05360446
Recruitment Status : Recruiting
First Posted : May 4, 2022
Last Update Posted : October 3, 2022
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.

Condition or disease Intervention/treatment Phase
Coronary Artery Disease Drug: Inclisiran sodium 300 mg Drug: Placebo Phase 3

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 600 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Multi-center, randomized, double-blind, placebo-controlled, parallel-group
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Sponsor personnel participating in the study conducted will be blinded also.
Primary Purpose: Treatment
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)
Actual Study Start Date : July 8, 2022
Estimated Primary Completion Date : July 18, 2025
Estimated Study Completion Date : July 18, 2025

Resource links provided by the National Library of Medicine


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.




Primary Outcome Measures :
  1. Percentage change in total coronary atheroma volume [ Time Frame: From baseline to month 24 ]
    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.


Secondary Outcome Measures :
  1. Percentage change in LDL-C [ Time Frame: From baseline to month 24 ]
    Full fasting lipid panel will be collected throughout the study beginning at baseline.

  2. Percentage change in low attenuation plaque volume evaluated by CCTA [ Time Frame: From baseline to month 24 ]
    Evaluating inclisiran compared to placebo in percentage change in low attenuation plaque volume evaluated by CCTA.

  3. Percentage of participants with progression, regression, or no change of total plaque atheroma volume [ Time Frame: From baseline to month 24 ]
    Evaluating inclisiran compared to placebo in percentage of participants experiencing progression, regression, or no change of total atheroma volume.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05360446


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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United States, Alaska
Novartis Investigative Site Recruiting
Anchorage, Alaska, United States, 99508
United States, California
Novartis Investigative Site Recruiting
Beverly Hills, California, United States, 90210
Novartis Investigative Site Recruiting
Torrance, California, United States, 90509-2910
United States, New York
Novartis Investigative Site Recruiting
New York, New York, United States, 10029
United States, Ohio
Novartis Investigative Site Recruiting
Canton, Ohio, United States, 44710
United States, Texas
Novartis Investigative Site Recruiting
Dallas, Texas, United States, 75226
Australia, Queensland
Novartis Investigative Site Recruiting
Auchenflower, Queensland, Australia, 4066
Australia, South Australia
Novartis Investigative Site Recruiting
Leabrook, South Australia, Australia, 5068
Australia, Western Australia
Novartis Investigative Site Recruiting
Murdoch, Western Australia, Australia, 6150
Belgium
Novartis Investigative Site Recruiting
Genk, Belgium, 3600
Novartis Investigative Site Recruiting
Hasselt, Belgium, 3500
Novartis Investigative Site Recruiting
Turnhout, Belgium, 2300
France
Novartis Investigative Site Recruiting
Paris, France, 75015
Novartis Investigative Site Recruiting
Paris, France
Novartis Investigative Site Recruiting
Poitiers, France, 86021
Novartis Investigative Site Recruiting
Toulouse Cedex, France, 31059
Hungary
Novartis Investigative Site Recruiting
Budapest, Hungary, 1085
Ireland
Novartis Investigative Site Recruiting
Galway, Ireland
Italy
Novartis Investigative Site Recruiting
Rozzano, MI, Italy, 20089
Spain
Novartis Investigative Site Recruiting
Barcelona, Spain, 08041
Novartis Investigative Site Recruiting
Madrid, Spain, 28034
Novartis Investigative Site Recruiting
Madrid, Spain, 28040
United Kingdom
Novartis Investigative Site Recruiting
Edinburgh, United Kingdom, EH16 4SA
Sponsors and Collaborators
Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT05360446    
Other Study ID Numbers: CKJX839D12303
2021-004601-47 ( EudraCT Number )
First Posted: May 4, 2022    Key Record Dates
Last Update Posted: October 3, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Inclisiran
KJX839
Atherosclerotic plaques
CCTA
CT-adapted Leaman score
LDL-C
FFRct
NOCAD
PCSK9 inhibitor
TAV
Additional relevant MeSH terms:
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Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Plaque, Atherosclerotic
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Pathological Conditions, Anatomical