E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Atherosclerotic cardiovascular disease (ASCVD) |
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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 |
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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 | 26.0 |
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 |
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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) |
|
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. To evaluate the safety and tolerability of inclisiran compared to placebo. |
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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. |
|
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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to the first occurrence of 3P-MACE |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From randomization to the first occurrence of 3P-MACE |
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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. Number of participants with SAEs. Number of participants with AEs leading to study treatment discontinuation. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From randomization to the occurrence of the secondary endpoint(s) |
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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 | 12 |
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 |
Argentina |
Australia |
Brazil |
Canada |
Chile |
China |
Colombia |
India |
Israel |
Japan |
Kenya |
Korea, Republic of |
Malaysia |
Mexico |
New Zealand |
Philippines |
Singapore |
South Africa |
Taiwan |
Thailand |
United States |
Russian Federation |
Turkey |
Serbia |
Mauritius |
Austria |
Belgium |
Bulgaria |
Croatia |
Czechia |
Denmark |
Estonia |
Finland |
France |
Hungary |
Italy |
Latvia |
Lithuania |
Netherlands |
Norway |
Poland |
Portugal |
Romania |
Slovakia |
Slovenia |
Spain |
Sweden |
|
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
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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 | 1 |
E.8.9.1 | In the Member State concerned days | 14 |
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 |