E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Atherosclerotic cardiovascular disease (ASCVD) |
Maladie cardiovasculaire athéroscléreuse |
|
E.1.1.1 | Medical condition in easily understood language |
Circulatory problems (such as heart attacks and strokes) caused by narrowing of the vessels supplying blood to the brain, heart and other organs |
Problèmes circulatoires (tels que les crises cardiaques et les accidents vasculaires cérébraux) causés par le rétrécissement des vaisseaux alimentant en sang le cerveau, le cœur et d'autres organes
|
|
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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10051615 |
E.1.2 | Term | Atherosclerotic cardiovascular disease |
E.1.2 | System Organ Class | 100000004866 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Inclisiran compared to placebo in reducing the risk of 3P-MACE (composite of CV death, non-fatal MI and non-fatal ischemic stroke) in participants with established ASCVD and a LDL-C ≥1.8 mmol/L (70 mg/dL) |
Démontrer la supériorité de l’inclisiran par rapport au placebo dans la réduction du risque de 3P-MACE (critère composite associant décès d'origine CV, IM non fatal et AVC ischémique non fatal) chez des patients atteints d’ASCVD établie avec un LDL-C ≥ 1,8 mmol/L (70 mg/dL). |
|
E.2.2 | Secondary objectives of the trial |
Inclisiran compared to placebo in reducing the risk of CV death.
Inclisiran compared to placebo in reducing the risk of 4P-MACE (composite of CV death, non-fatal MI, non-fatal ischemic stroke and urgent coronary revascularization).
Inclisiran compared to placebo in reducing the risk of all-cause death. |
Démontrer la supériorité de l'inclisiran par rapport au placebo dans la réduction du risque
de décès d'origine CV ;
Démontrer la supériorité de l'inclisiran par rapport au placebo dans la réduction du risque
d'événement du critère 4P-MACE (critère composite associant décès d'origine CV, IM non
fatal, AVC ischémique non fatal et revascularisation coronaire en urgence) ;
Evaluer l'inclisiran par rapport au placebo dans la réduction du risque de décès toutes
causes confondues. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female ≥40 years of age
- Fasting LDL-C ≥1.8 mmol/L (70 mg/dL) at the Screening Visit
- At the Screening Visit, participants must be on a stable (≥4 weeks) and well-tolerated lipid-lowering regimen (including e.g. with or without Ezetimibe) that must include a high-intensity statin therapy with either atorvastatin ≥40 mg QD or rosuvastatin ≥20 mg QD
- Established CV disease, defined as any of the following:
- Previous myocardial infarction
- Previous ischemic stroke
- Symptomatic peripheral arterial disease (PAD), as evidenced by either intermittent claudication with ABI <0.85, prior peripheral arterial revascularization procedure, or, amputation due to atherosclerotic disease
Other inclusion criteria are listed in the clinical study protocol. |
- Patient de sexe masculin ou féminin, âgé d’au moins 40 ans à la signature du consentement éclairé
- LDL-C ≥ 1.8 mmol/L (70 mg/dL) à jeun lors de la visite de sélection, mesuré au laboratoire central
- Lors de la visite de sélection, les patients doivent suivre un régime hypolipémiant stable (≥ 4 semaines) et bien toléré (y compris, par ex. avec ou sans ézétimibe) qui doit inclure un traitement par statine de forte intensité, avec atorvastatine ≥ 40 mg QD ou rosuvastatine ≥ 20 mg QD
- Maladie CV caractérisée, définie comme une des trois pathologies suivantes :
- Infarctus du myocarde antérieur
- AVC ischémique antérieur
- Maladie artérielle périphérique symptomatique, comme en témoigne une claudication intermittente avec indice de pression systolique (IPS) < 0,85, une procédure antérieure de revascularisation artérielle périphérique, ou une amputation due à une maladie artérioscléreuse.
D'autres critères d'inclusion sont listés dans le protocole de l'étude clinique. |
|
E.4 | Principal exclusion criteria |
- New York Heart Association (NYHA) class III or IV heart failure at the Statin Optimization Screening Visit (if applicable), Screening Visit, or at the Baseline Visit (Day1)
- Previous exposure to inclisiran or any other non-mAb PCSK9-targeted therapy, either as an investigational or marketed drug within 2 years prior to the first study visit
- Pregnant or nursing (lactating) women
- Women of child-bearing potential, unless they are using effective methods of contraception during dosing of study treatment
Other exclusion criteria are listed in the clinical study protocol. |
- Insuffisance cardiaque de classe NYHA III ou IV lors de la visite de sélection pour l’optimisation des statines (le cas échéant), de la visite de sélection ou de la visite baseline (jour 1)
- Exposition antérieure à l'inclisiran ou à tout autre traitement anti-PCSK9 non-anticorps monoclonal, expérimental ou commercialisé, dans les 2 ans précédant la première visite d'étude
- Grossesse ou allaitement
- Femmes en âge de procréer, sauf si elles utilisent des moyens de contraception efficaces pendant toute la durée du traitement à l'étude.
D'autres critères d'exclusion sont listés dans le protocole de l'étude clinique. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Time to the first occurrence of 3P-MACE |
Délai jusqu'à la survenue du critère 3P-MACE (évènement cardiovasculaire majeur) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
From randomization to the first occurrence of 3P-MACE |
De la randomisation à l'apparition du 3P-MACE |
|
E.5.2 | Secondary end point(s) |
Time to occurrence of CV death.
Time to the first occurrence of 4P-MACE.
Time to the occurrence of all-cause death. |
Délai jusqu'au décès d'origine cardiovasculaire
Délai jusqu'à la survenue du critère 4P-MACE
Délai jusqu'au décès quelque soit la cause |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
From randomization to the occurrence of the secondary endpoint(s) |
De la randomisation à la survenue du ou des critère(s) secondaire(s) |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 17 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 363 |
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 | No |
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 |
Australia |
Bosnia and Herzegovina |
Brazil |
Canada |
Chile |
China |
Colombia |
Georgia |
India |
Israel |
Japan |
Kenya |
Korea, Republic of |
Malaysia |
Mauritius |
Mexico |
New Zealand |
Philippines |
Russian Federation |
Singapore |
South Africa |
Taiwan |
Thailand |
Turkey |
Ukraine |
United States |
Austria |
Belgium |
Bulgaria |
Croatia |
Denmark |
Estonia |
France |
Germany |
Hungary |
Italy |
Latvia |
Lithuania |
Netherlands |
Poland |
Portugal |
Romania |
Slovakia |
Slovenia |
Spain |
Sweden |
Czechia |
Argentina |
|
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 |
Dernière visite du dernier patient |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |