Clinical Trials Register

Summary
EudraCT Number:	2021-004601-47
Sponsor's Protocol Code Number:	CKJX839D12303
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2022-04-04
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Belgium - FPS Health-DGM

A.2

EudraCT number

2021-004601-47

A.3

Full title of the trial

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)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Coronary computed tomography study to assess the effect of inclisiran on atherosclerotic plaque progression in participants with a diagnosis of non-obstructive coronary artery disease without previous cardiovascular events

A.3.2

Name or abbreviated title of the trial where available

VICTORION-PLAQUE

A.4.1

Sponsor's protocol code number

CKJX839D12303

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Novartis Pharma AG
B.1.3.4	Country	Switzerland
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Novartis Pharma AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Pharma AG
B.5.2	Functional name of contact point	Clinical Trial Information Desk
B.5.3	Address:
B.5.3.1	Street Address	Forum 1, Novartis Campus
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4056
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	+41 61 324 1111
B.5.5	Fax number	+41 61 324 8001
B.5.6	E-mail	clinicaltrial.enquiries@novartis.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Leqvio 284 mg solution for injection in pre-filled syringe
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Inclisiran
D.3.2	Product code	KJX839
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	INCLISIRAN
D.3.9.1	CAS number	1639324-62-1
D.3.9.2	Current sponsor code	KJX839
D.3.9.3	Other descriptive name	Inclisiran sodium
D.3.9.4	EV Substance Code	SUB182427
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection in pre-filled syringe
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Non-obstructive coronary artery disease

E.1.1.1

Medical condition in easily understood language

atherosclerotic plaque (fatty deposits that can lead to heart disease) in the heart with less than 50% obstruction of blood flow

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10011078
E.1.2	Term	Coronary artery disease
E.1.2	System Organ Class	10007541 - Cardiac disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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

E.2.2

Secondary objectives of the trial

- 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 Statistical analysis plan (SAP)
- Assess the safety and tolerability profile of inclisiran

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written informed consent must be obtained before any assessment is performed.
2. Male or female ≥18 to ≤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 (2.6 mmol/L) if on statin therapy but not on a maximally tolerated statin therapy; ii) ≥150 mg/dL (3.9 mmol/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.Local laboratory values should be calculated using the Friedewald formula for consistency across study sites if the Screening visit occurs prior to the Baseline CCTA Visit. If the Screening and Baseline Visits occur on the same day, then the LDL-C value will be assessed on the central laboratory sample. If the center can only perform the direct LDL-C test, then the local lab should also obtain the total cholesterol, HDL-C, and triglycerides results so that the LDL-C can be calculated using the Friedewald estimation.
4. 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. Local laboratory values should be calculated using the Friedewald formula for
consistency across study sites. If the center can only perform the direct LDL-C test, then the local lab should also obtain the total cholesterol,
HDL-C, and triglycerides results so that the LDL-C can be calculated using the Friedewald estimation.
5. 5. Participants having Non-Obstructive Coronary Artery (NOCAD)*
without previous cardiovascular events: NOCAD is defined as:
(1) Participants with a CT-adapted Leaman score >5 and a diameter
stenosis <50%***
OR
(2) Participants with a CT-adapted Leaman score >5 and a diameter
stenosis ≥50%*but with FFRCT ≥0.76**. Notes: *=In case of left main
CAD, diameter stenosis is ≥40%. **=In case of FFRCT between ≥0.76
and 0.80, participant eligibility will be assessed and determined by the
Imaging Core Lab based on the location of the lesion, proximality of the
lesion, delta FFRCT, and diffuseness of coronary artery disease
FFRCT and CT-adapted Leaman score will be determined by the Imaging
Core Lab.
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 as described above and as assessed by
the Imaging Core Lab.

6. 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.

7. 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 LDL-C value at the Baseline Visit does not meet
eligibility, the eligibility will be determined based on the central lab
result.
8.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.

E.4

Principal 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. Uncontrolled severe hypertension: mean systolic blood pressure >180
mmHg or mean diastolic blood pressure >110 mmHg prior to
randomization (assessed at the Screening Visit) despite antihypertensive
therapy.
10. Heart failure New York Heart Association (NYHA) class III or class IV
at the Screening Visit.
11. 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.
12. Active liver disease defined as any known current infectious,
neoplastic, or metabolic pathology of the liver at the Screening Visit.
Participants who enter Screening or the Statin Optimization Visit must
have AST and ALT ≤3x ULN to be allowed to continue in the Screening or
Statin Optimization Period.
13.Local creatine kinase (CK) values of either, unless a more stringent
threshold is mandated by a local regulatory authority (e.g., ≥3x ULN in
Korea according to MFDS internal guideline):
• CK values ≥5x ULN at the Screening Visit for participants on
maximally tolerated statin therapy or who are statin intolerant.
• CK values ≥5x ULN at Screening and before entering the Statin
Optimization Period and confirmed by repeat test within 7 days at
Screening or based on Investigator's judgement for participants entering
the Statin Optimization Period (who will be switched to or initiated on
the protocol-specified dose of high-intensity statin of atorvastatin ≥40
mg QD or rosuvastatin ≥20 mg QD during the Statin Optimization
Period).
14. Local CK values ≥5x ULN at the Statin Optimization 3 Visit unless a
more stringent threshold is mandated by a local regulatory authority
(e.g., ≥3x ULN in Korea according to MFDS internal guideline) and
monitored according to national guidelines and statin label during the
Statin Optimization Period.
15. Participant with myopathy at the Statin Optimization 3 Visit.
Please refer to Section 5.2 of the study protocol for the complete list of
exclusion criteria

E.5 End points

E.5.1

Primary end point(s)

Percentage change from baseline to month 24 in total coronary atheroma volume

E.5.1.1

Timepoint(s) of evaluation of this end point

From baseline to month 24.

E.5.2

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
-Incidence, severity, and relationship to study drug of TEAEs and Serious
Adverse Events (SAEs)

E.5.2.1

Timepoint(s) of evaluation of this end point

From baseline to month 24.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Argentina

Chile

Switzerland

Australia

Brazil

Canada

China

India

Japan

Korea, Republic of

United Kingdom

United States

Belgium

France

Germany

Hungary

Ireland

Italy

Spain

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

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

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

223

F.4.2.2

In the whole clinical trial

600

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

A post trial access program may be initiated to allow for the investigational drug to be made available to qualified patients participating in the study, in countries where it is not commercially available at the time of study completion.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2022-04-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-07-01

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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IMP with orphan designation in the indication
Orphan Designation Number:
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