E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Familial Hypercholesterolemia |
Hipercolesterolemia familiar |
|
E.1.1.1 | Medical condition in easily understood language |
Familial Hypercholesterolemia |
Hipercolesterolemia familiar |
|
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 |
|
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 |
El objetivo principal del estudio es evaluar la seguridad y la tolerabilidad a largo plazo de inclisirán en participantes con HFHe o HFHo. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the long-term effect of inclisiran treatment on LDL-C levels |
Evaluar el efecto a largo plazo del tratamiento con inclisirán en los niveles de colesterol de lipoproteína de baja densidad (C-LDL). |
|
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 |
- Participantes de ambos sexos con un diagnóstico de HFHe o HFHo que hayan finalizado los estudios ORION-16 u ORION-13, entendiendo por ello que hayan recibido la última dosis del fármaco del estudio y hayan completado la visita final del estudio según el protocolo correspondiente. - Según el criterio clínico del investigador, los participantes deben haberse beneficiado del tratamiento con inclisirán en los estudios ORION-16 u ORION-13. - Continuar recibiendo en la actualidad tratamientos hipolipemiantes (p. ej., estatinas o ezetimiba) del estudio principal sin ningún cambio previsto en la medicación ni en la dosis durante la participación en el estudio. |
|
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 |
- Participantes que en los estudios principales ORION-16 y ORION-13 realizados con inclisirán se hayan considerado fallo de selección o hayan discontinuado permanentemente el tratamiento/estudio por cualquier motivo o bien que hayan presentado problemas graves de seguridad o tolerabilidad relacionados con el tratamiento con inclisirán. - Cualquier enfermedad no controlada o grave, o cualquier condición médica, física o quirúrgica que pueda interferir en la participación en el estudio clínico o en la interpretación de los resultados del mismo, o que implique un riesgo significativo para el participante. - Enfermedad hepática activa definida como cualquier patología infecciosa, neoplásica o metabólica actual del hígado. |
|
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 |
Incidencia, gravedad y relación con el fármaco del estudio de acontecimientos adversos que han aparecido con el tratamiento (AAAT) y acontecimientos adversos graves que han aparecido con el tratamiento (AAGAT); constantes vitales; parámetros de laboratorio. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
From day 1 to the end of study |
Desde el día 1 hasta el fin de estudio |
|
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) |
Cambio porcentual y cambio absoluto en el C-LDL respecto a la basal del estudio principal hasta el fin de estudio (EoS). |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
End of study |
Fin de estudio |
|
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 |
Tolerability |
Tolerabilidad |
|
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 | 4 |
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
|
LPLV |
última visita último paciente |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 22 |
E.8.9.2 | In all countries concerned by the trial years | 5 |