E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Heterozygous Familial Hypercholesterolemia or Non-Familial Hypercholesterolemia with High and Very High Cardiovascular Risk |
|
E.1.1.1 | Medical condition in easily understood language |
Hypercholesterolemia, also called dyslipidemia, is the presence of high
levels of cholesterol in the blood |
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E.1.1.2 | Therapeutic area | Body processes [G] - Metabolic Phenomena [G03] |
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 | 10054380 |
E.1.2 | Term | Familial hypercholesterolemia |
E.1.2 | System Organ Class | 100000004850 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020604 |
E.1.2 | Term | Hypercholesterolemia |
E.1.2 | System Organ Class | 100000004861 |
|
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 | 10068617 |
E.1.2 | Term | Coronary heart disease |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10007649 |
E.1.2 | Term | Cardiovascular disorder |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
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 |
|
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 neurocognitive function
with use of Praluent after 96 weeks of treatment versus placebo |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives are:
• To evaluate the effect of Praluent in comparison with placebo on
lipoproteins
• To evaluate the safety and tolerability of Praluent |
|
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 |
An optional genomic sub-study will be conducted to identify genetic associations with clinical or biomarker response to PCSK9 inhibition, hyperlipidemia, or CVD. If necessary, samples may also be used to identify markers associated with toxicity |
|
E.3 | Principal inclusion criteria |
1. Men and women ≥ age 40 and ≤ age 85
2. Patients with heFH or non-FH patients at high or very high cardiovascular risk
3. Patients with history of CHD not having adequate control of their hypercholesterolemia with LDL-C ≥70 mg/dL, or all other patients with LDL-C ≥100 mg/dL and be on a maximally-tolerated dose of statin (unless they are statin-intolerant) for at least 28 days prior to the screening visit.
4. Patients must have successfully completed the Motor Screening Task
|
|
E.4 | Principal exclusion criteria |
1. Patients with known Alzheimer’s disease or other dementia, schizophrenia, bipolar disorder, severe depression (≥11 score of the Geriatric Depression Scale short form [GDS-S; Appendix 8]), cognitive impairment (<26 score of the Montreal Cognitive Assessment [MoCA]; Appendix 9]), or patients with a sleep disorder requiring daily pharmacological treatment
2. Patients >85 year old
3. Patient with a hemorrhagic stroke within last 5 years
4. History of a myocardial infarction, unstable angina leading to hospitalization, coronary artery bypass graft surgery, percutaneous coronary intervention, uncontrolled cardiac arrhythmia, carotid surgery or stenting, stroke, transient ischemic attack, or carotid revascularization within 3 months prior to the screening visit, or endovascular procedure or surgical intervention for peripheral vascular disease within 3 months prior to the
screening visit.
5. eGFR <30 mL/min/1.73 m2 according to 4-variable Modification of Diet in Renal Disease Study equation (calculated by a central lab).
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure is the change in Cambridge Neuropsychological Test Automated Battery (CANTAB) cognitive domain Spatial Working Memory (SWM) strategy score from baseline to week 96. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Screening, Baseline, Week 24, Week 48, Week 72 and Week 96/End of Study |
|
E.5.2 | Secondary end point(s) |
• The percent change in lipoproteins
• The proportion of patients reaching LDL-C <70 mg/dL or LDL-C <50 mg/dL
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
From baseline to weeks 12, 24, 48, 72, and 96 |
|
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | 20 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 34 |
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 |
Bulgaria |
Chile |
Colombia |
Estonia |
Israel |
Japan |
Mexico |
Peru |
Russian Federation |
Slovakia |
South Africa |
Ukraine |
United States |
|
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 | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |