E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cardiovascular Disease |
Maladie cardiovasculaire |
|
E.1.1.1 | Medical condition in easily understood language |
Atherosclerosis |
Athérosclérose |
|
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 | 10051614 |
E.1.2 | Term | Arteriosclerotic 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 |
The primary objectives of this study is to demonstrate the superiority of pelacarsen (TQJ230) compared to placebo in reducing the risk of expanded MACE (cardiovascular death, non-fatal MI, non-fatal stroke and urgent coronary re-vascularization requiring hospitalization) in 1) the overall study population with established CVD (Lp(a) ≥ 70 mg/dL) and/or 2) in a subpopulation with established CVD and Lp(a) ≥ 90 mg/dL. |
L'objectif primaire de cette étude est de démontrer la supériorité du pelacarsen (TQJ230) sur le placebo dans la réduction du risque d'événement MACE élargi (mort cardiovasculaire, IM non fatal, accident vasculaire cérébral non fatal et revascularisation coronaire urgente nécessitant une hospitalisation) dans 1) l'ensemble de la population de l'étude présentant une MCV établie et un taux de Lp(a) ≥ 70 mg/dl et/ou 2) dans une sous-population présentant une MCV établie et un taux de Lp(a) ≥ 90 mg/dl |
|
E.2.2 | Secondary objectives of the trial |
In the overall trial population and in subpopulation (≥ 90 mg/dL):
Demonstrate the superiority of pelacarsen (TQJ230) compared to placebo in reducing the risk of the MACE composite of CV death, non-fatal MI and non-fatal stroke.
Demonstrate the superiority of pelacarsen (TQJ230) compared to placebo in reducing the risk of the composite of coronary heart disease (CHD) outcomes: death due to CHD, non-fatal MI and urgent coronary re-vascularization requiring hospitalization .
Evaluate the rate of all cause death.
Demonstrate the superiority of pelacarsen (TQJ230) compared to
placebo in lowering the Lp(a) level at 1 year. |
Dans l'ensemble de la population de l’étude et dans la sous-population (≥ 90 mg/dl) :
Démontrer la supériorité du pelacarsen (TQJ230) sur le placebo à réduire le risque du critère composite MACE associant décès d'origine CV, IM non fatal et d'accident vasculaire cérébral non fatal.
Démontrer la supériorité du pelacarsen (TQJ230) sur le placebo à réduire le risque du critère composite de maladie coronarienne : décès par cardiopathie congénitale, IM non fatal et revascularisation coronaire urgente nécessitant une hospitalisation.
Evaluer le taux de décès toutes causes confondues.
Démontrer la supériorité du pelacarsen (TQJ230) sur le placebo pour diminuer le Lp(a) à 1 an |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Lp(a) ≥ 70 mg/dL at the screening visit
- Optimal LDL-cholesterol lowering treatment
- Optimal treatment of other CV risk factors
- Myocardial infarction: ≥ 3 months from screening and randomization
visits to ≤ 10 years prior to the screening visit, and/or
- Ischemic stroke: ≥ 3 months from screening and randomization visits
to ≤ 10 years prior to the screening visit
- Clinically significant symptomatic peripheral artery disease |
- Lp(a) ≥ 70 mg/dl lors de la visite de sélection
- Traitement optimal visant à réduire le LDL-cholestérol
- Traitement optimal pour les autres facteurs de risque CV
- Infarctus du myocarde : ≥ 3 mois à ≤ 10 ans avant la période de sélection
- AVC ischémique : ≥ 3 mois à ≤ 10 ans avant la période de sélection
- Maladie artérielle périphérique symptomatique cliniquement significative |
|
E.4 | Principal exclusion criteria |
- Uncontrolled hypertension
- Heart failure New York Heart Association (NYHA) class IV
- History of malignancy of any organ system
- History of hemorrhagic stroke or other major bleeding
- Platelet count <140,000 per mm3
- Active liver disease or hepatic dysfunction
- Significant kidney disease
- Pregnant or nursing women |
- Hypertension non contrôlée
- Insuffisance cardiaque, classe IV de la New York Heart Association (NYHA)
- Antécédents de tumeur maligne de tout système d'organes
- Antécédents d'accident vasculaire cérébral hémorragique ou d'autres saignements majeurs
- Nombre de plaquettes <140,000 per mm3
- Maladie hépatique active ou dysfonctionnement hépatique
- Maladie glomérulaire significative
- Grossesse ou allaitement |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1. Time to first occurrence of clinical endpoint committee confirmed expanded major adverse cardiovascular events in patients with elevated Lp(a) ≥ 70 mg/dL
2.Time to the first occurrence of clinical endpoint committee confirmed expanded major adverse cardiovascular events in a population of patients with elevated Lp(a) ≥ 90 mg/dL. |
1. Délai jusqu’à la première occurrence du critère d'évaluation confirmé par le Comité d’adjudication des événements cardiovasculaires, dans une population de patients présentant un taux de Lp(a) élevé ≥ 70 mg/dl.
2. Délai jusqu’à la première occurrence du critère d'évaluation confirmé par le Comité d’adjudication des événements cardiovasculaires, dans une sous-population de patients présentant un taux de Lp(a) élevé ≥ 90 mg/dl. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
4.25 years for both endpoints |
4,25 ans pour les deux critères |
|
E.5.2 | Secondary end point(s) |
1.Time to the first occurrence of the clinical endpoint committee confirmed composite endpoint of major adverse cardiovascular events (CV death, non-fatal MI, and non-fatal stroke)
2.Time to the first occurrence of the clinical endpoint committee confirmed composite endpoint of coronary heart disease: coronary heart disease death, non-fatal MI, urgent coronary re-vascularization requiring hospitalization
3.Change in Lp(a) in the log scale from baseline at 1 year
4.CEC confirmed all-cause death from randomization to the end of study |
1. Délai jusqu’à la première occurrence du critère d'évaluation confirmé par le Comité d’adjudication des événements cardiovasculaires (décès d’origine CV, IM non fatal et accident vasculaire cérébral non fatal).
2. Délai jusqu’à la première occurrence du critère composite de maladies coronariennes (CHD) confirmé par le CEC : Décès dû à une maladie coronarienne (CHD), IM non fatal, revascularisation coronaire urgente nécessitant une hospitalisation.
3. Variation due la Lp(a) ensur l’échelle logarithmique à 1 an par rapport à la baseline
4.Décès toutes causes confondues confirmé par le CEC entre la randomisation et la fin de l'étude. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
4.25 years for endpoints 1,2 and 4
1 year for endpoint 3 |
4,25 ans pour critères 1, 2 and 4
1 an pour critère 3 |
|
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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
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 | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 395 |
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 |
Brazil |
Canada |
Chile |
China |
Colombia |
Guatemala |
Hong Kong |
India |
Israel |
Japan |
Korea, Republic of |
Lebanon |
Mexico |
Peru |
Philippines |
Russian Federation |
South Africa |
Taiwan |
Turkey |
United States |
Austria |
Belgium |
Bulgaria |
Denmark |
France |
Germany |
Greece |
Hungary |
Iceland |
Italy |
Netherlands |
Norway |
Poland |
Portugal |
Romania |
Slovakia |
Spain |
Sweden |
Switzerland |
United Kingdom |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |