E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Heterozygous Familial Hypercholesterolemia |
|
E.1.1.1 | Medical condition in easily understood language |
Heterozygous Familial Hypercholesterolemia |
|
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 | 10057079 |
E.1.2 | Term | Heterozygous familial hypercholesterolemia |
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 |
Demonstrate superiority of inclisiran compared to placebo in reducing LDL-C [percent change] at Day 330 (Year 1) |
Démontrer la supériorité de l’inclisiran par rapport au placebo en termes de diminution du cholestérol LDL exprimée par la variation en pourcentage de changement au Jour 330 (Année 1). |
|
E.2.2 | Secondary objectives of the trial |
- Demonstrate superiority of inclisiran compared to placebo in reducing LDL-C [time-adjusted percent change] over Year 1
- Demonstrate superiority of inclisiran compared to placebo in reducing LDL-C [absolute change] at Day 330 (Year 1)
- Demonstrate superiority of inclisiran compared to placebo in reducing Apo B, lipoprotein (a) [Lp(a)], non-high density lipoprotein cholesterol (non-HDL-C), and total cholesterol [percent change] at Day 330 (Year 1) - Hierarchical testing
Other secondary objectives are stated in the clinical study protocol |
-Démontrer la supériorité de l’inclisiran par rapport au placebo en termes de diminution du cholestérol LDL exprimée par la variation en pourcentage ajustée au cours du temps sur l’Année 1
-Démontrer la supériorité de l’inclisiran par rapport au placebo en termes de diminution du cholestérol LDL exprimée par la variation absolue au Jour 330 (Année 1)
-Démontrer la supériorité de l’inclisiran par rapport au placebo en termes de diminution de l’apolipoprotéineB (Apo B), de la lipoprotéine (a) [Lp(a)], du cholestérol non-HDL (pour high density lipoprotein) et du cholestérol total, exprimée par la variation en pourcentage au Jour 330 (Année 1)
D'autres objectifs secondaires sont énoncés dans le protocole de l'étude clinique |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Additional PK sampling in a subset of participants |
Échantillonnage PK supplémentaire dans un sous-ensemble de participants |
|
E.3 | Principal inclusion criteria |
• Heterozygous Familial Hypercholesterolemia (HeFH) diagnosed either by genetic testing or on phenotypic criteria
• Fasting LDL-C >130 mg/dL (3.4 mmol/L) at screening
• Fasting triglycerides <400 mg/dL (4.5 mmol/L) at screening
• On maximally tolerated dose of statin (investigator’s discretion) with or without other lipid-lowering therapy; stable for ≥ 30 days before screening
• Estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2 at screening
Other inclusion criteria are listed in the clinical study protocol |
- HF hétérozygote diagnostiquée soit par un test génétique soit sur des critères phénotypiques
- Taux de cholestérol LDL à jeun > 130 mg/ml (3,4 mmol/l) à la visite de sélection, mesuré par le laboratoire central.
- Taux de triglycérides à jeun < 400 mg/dl (4,5 mmol/l) à la visite de sélection, mesuré par le laboratoire central.
- La dose du traitement hypolipémiant (statines et/ou ézétimibe) doit être stable depuis ≥ 30 jours avant la sélection, sans modification prévue du traitement ou de la dose pendant la durée de participation à l’étude.
- Débit de filtration glomérulaire estimé > 30 ml/min/1,73 m² au moment de la sélection.
D'autres critères d'inclusion sont listés dans le protocole de l'étude clinique |
|
E.4 | Principal exclusion criteria |
• Homozygous familial hypercholesterolemia (HoFH)
• Active liver disease
• Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome
• Major adverse cardiovascular events within 3 months prior to randomization
• Previous treatment with monoclonal antibodies directed towards PCSK9 (within 90 days of screening)
• Recent and/or planned use of other investigational medicinal products or devices
Other exclusion criteria are listed in the clinical study protocol |
- HF homozygote.
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- Hypercholestérolémie secondaire, par exemple liée à une hypothyroïdie ou un syndrome néphrotique.
- Accidents cardiovasculaires majeurs dans les 3 mois précédant la randomisation.
- Traitement antérieur (dans les 90 jours avant la sélection) par anticorps monoclonaux dirigés contre la PCSK9
- Utilisation prévue d’un traitement expérimental ou d’un dispositif médical expérimental pendant la durée de participation à l’étude. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Percentage (%) change in low-density lipoprotein cholesterol (LDL-C) |
Variation en pourcentage du cholestérol LDL |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
baseline to Day 330 |
Entre la baseline et le Jour 330 |
|
E.5.2 | Secondary end point(s) |
- Time-adjusted % change in LDL-C
- Absolute change in LDL-C
- % change in apolipoprotein B (Apo B), lipoprotein (a) [Lp (a)], non-high density lipoprotein cholesterol (non-HDL-C), and total cholesterol
Other secondary endpoint can be found in the clinical study protocol |
- Variation en pourcentage du cholestérol LDL
- Variation absolue du cholestérol LDL
- Variation en pourcentage de l’Apo B, de la Lp(a), du cholestérol non-HDL et du cholestérol total |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Baseline, after Day 90 up to Day 330
- Baseline and Day 330
- Baseline and Day 330 |
- baseline après le Jour 90 et jusqu'au Jour 330
- baseline et le Jour 330
- baseline et le Jour 330 |
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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 | 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 | 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 | 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 | 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 42 |
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 |
Russian Federation |
Serbia |
South Africa |
Taiwan |
Turkey |
United States |
France |
Germany |
Greece |
Hungary |
Italy |
Netherlands |
Slovenia |
Spain |
Switzerland |
United Kingdom |
|
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 | 2 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 21 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 9 |