Study with Inclisiran or placebo in individuals with non-obstructive coronary artery disease without prior cardiovascular events (VICTORION-PLAQUE)

ID di studio ICTRP
EUCTR2021-004601-47 (ICTRP)

Titolo ufficiale (approvato dal comitato etico)
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) (BASEC)

Titolo accademico
A multi-center, randomized, double-blind, placebo controlled, parallelgroup 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) - VICTORION-PLAQUE (ICTRP)

Titolo pubblico
Coronary computed tomography study to assess the effect of inclisiran on atherosclerotic plaque progression in participants with a diagnosis of nonobstructivecoronary artery disease without previous cardiovascular events (ICTRP)

Malattie studiate
Non-obstructive coronary artery disease
MedDRA version: 20.0Level: PTClassification code 10011078Term: Coronary artery diseaseSystem Organ Class: 10007541 - Cardiac disorders;Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14] (ICTRP)

Intervento studiato

Trade Name: Leqvio 284 mg solution for injection in pre-filled syringe
Product Name: Inclisiran
Product Code: [KJX839]
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: INCLISIRAN
CAS Number: 1639324-62-1
Current Sponsor code: KJX839
Other descriptive name: Inclisiran sodium
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

(ICTRP)

Tipo di studio
Interventional clinical trial of medicinal product (ICTRP)

Disegno dello studio
Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2 (ICTRP)

Criteri di inclusione/esclusione
Gender:
Female: yes
Male: yes

Inclusion criteria:
1. Written informed consent must be obtained before any assessment is performed.
2. Male or female =18 years or =80 years of age at signing of informed consent.
3. 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.
4. 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)
5. 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.
6. Participants having 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.
7. 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 330
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 270
(ICTRP)

Exclusion criteria:
1. Previous myocardial infarction (MI), or prior coronary revascularization [percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG)].
2. Planned revascularization (PCI or CABG).
3. Previous ischemic cerebrovascular event 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.
4. 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.
5. 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.
6. NOCA participant who was prescreened by the Investigator with visual diameter stenosis >50% but FFR <0.8.
7. 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.
8. Pacemaker or implantable cardioverter-defibrillator (ICD) in situ.
9. Systolic Left Ventricle Ejection Fraction <30% at the Screening Visit.
10. 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.
11. Heart failure New York Heart Association (NYHA) class III or class IV at the Screening Visit.
12. 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.
13. 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.

Please refer to Section 5.2 of the study protocol for the complete list of exclusion criteria


Endpoint primari e secondari
Main Objective: Inclisiran compared to placebo, on top of maximally tolerated statin therapy, in reducing the total coronary atheroma volume assessed by CCTA from baseline to month 24;Secondary Objective: - Inclisiran compared to placebo, administered on top of maximally tolerated statin therapy, in reducing the LDL-C from baseline to month 24
- Inclisiran compared to placebo in percentage change in low attenuation plaque volume evaluated by CCTA
- Inclisiran compared to placebo in percentage of participants experiencing progression, regression, or no change of total plaque atheroma volume (progression, regression, or no change will be defined in the SAP);Primary end point(s): Percentage change from baseline to month 24 in total coronary atheroma volume;Timepoint(s) of evaluation of this end point: From baseline to month 24. (ICTRP)

Timepoint(s) of evaluation of this end point: From baseline to month 24.;Secondary end point(s): -percentage change in LDL-C from baseline to month 24
-percentage change in low attenuation plaque volume evaluated by CCTA
-percentage of participants with progression, regression, or no change of total plaque atheroma volume (ICTRP)

Data di registrazione
03.03.2022 (ICTRP)

Inclusione del primo partecipante
09.05.2022 (ICTRP)

Sponsor secondari
non disponibile

Contatti aggiuntivi
Regulatory Affairs, info.studiclinici@novartis.com, Novartis Farma S.p.A. (ICTRP)

ID secondari
CKJX839D12303 (ICTRP)

Risultati-Dati individuali dei partecipanti
non disponibile

Ulteriori informazioni sullo studio
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2021-004601-47 (ICTRP)