E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Familial Hypercholesterolemia |
Hypercholestérolémie familiale |
|
E.1.1.1 | Medical condition in easily understood language |
Familial Hypercholesterolemia |
Hypercholestérolémie familiale |
|
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 | LLT |
E.1.2 | Classification code | 10049593 |
E.1.2 | Term | Familial hypercholesterolaemia |
E.1.2 | System Organ Class | 100000004850 |
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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 |
The primary objective of the study is to evaluate the long-term safety and tolerability of inclisiran in participants with HeFH or HoFH |
L'objectif principal de l'étude est d'évaluer l'innocuité et la tolérance à long terme de l'inclisiran chez des patients atteints d'HFHe ou d'HFHo |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the long-term effect of inclisiran treatment on LDL-C levels |
Evaluer l'effet à long terme du traitement par inclisiran sur les taux de cholestérol à lipoprotéines de basse densité (LDL-C) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male and female participants with a diagnosis of HeFH or HoFH who completed the ORION-16 or ORION-13 studies, meaning the participant received the last dose of study drug and completed the final study visit as per applicable protocol • Per investigator`s clinical judgment, participant derived benefit from treatment with inclisiran in the ORION-16 or ORION-13 studies • Continuing current lipid-lowering therapies (such as e.g. statin and/or ezetimibe) from the feeder study with no planned medication or dose change during study participation
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• Patients de sexe masculin et féminin porteurs d’un diagnostic de HFHe ou HFHo qui ont terminé les études ORION-16 ou ORION-13, ce qui signifie que le patient a reçu la dernière dose du médicament à l'étude et a terminé la dernière visite de l'étude conformément au protocole applicable • Selon le jugement clinique de l'investigateur, le patient a tiré un bénéfice du traitement par inclisiran dans les études ORION-16 ou ORION-13 • Poursuite des traitements hypolipémiants en cours (par exemple, statines et/ou ézétimibe) pendant l'étude précédente sans changement de traitement ni de dose planifié. |
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E.4 | Principal exclusion criteria |
• Participants who in the preceding inclisiran ORION-16 and ORION-13 studies either screen failed or permanently discontinued from the treatment/study for any reason or had serious safety or tolerability issues related to inclisiran treatment • Any uncontrolled or serious disease, or any medical, physical or surgical condition, that may either interfere with participation in the clinical study or interpretation of clinical study results, and/or put the participant at significant risk • Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver |
• Patients qui, lors des études précédentes ORION-16 et ORION-13 avec l’inclisiran, ont été en échec de sélection ou ont arrêté prématurément le traitement ou l'étude pour une raison quelconque ou ont présenté de graves problèmes de sécurité ou de tolérance liés au traitement par inclisiran • Toute maladie incontrôlée ou grave, ou toute pathologie médicale, physique ou chirurgicale, susceptible de compromettre la participation à l'étude ou l'interprétation des résultats de l'étude et/ou d'exposer le patient à un risque important • Maladie hépatique active définie comme toute pathologie hépatique infectieuse, néoplasique ou métabolique en cours |
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E.5 End points |
E.5.1 | Primary end point(s) |
Incidence, severity and relationship to study drug of treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs); vital signs; laboratory parameters |
Incidence, gravité et relation avec le médicament à l'étude des événements indésirables liés au traitement (TEAE) et des événements indésirables graves (TESAE) ; signes vitaux; paramètres de laboratoire |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From day 1 to the end of study |
Du 1er jour à la fin d'étude |
|
E.5.2 | Secondary end point(s) |
Percentage change and absolute change in LDL-C from baseline in the feeder study to end of study (EoS) |
Changement en pourcentage et changement absolu du LDL-C entre le début de l'étude d'alimentation et la fin de l'étude (EoS) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
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 |
Brazil |
Canada |
Israel |
Lebanon |
Malaysia |
South Africa |
Taiwan |
United States |
France |
Poland |
Netherlands |
Spain |
Switzerland |
Germany |
Greece |
Italy |
Hungary |
Norway |
Russian Federation |
Slovenia |
Turkey |
United Kingdom |
|
E.8.7 | Trial has a data monitoring committee | No |
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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |