E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with CV-risk and statin intolerance due to statin-associated muscle symptoms (SAMS) |
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E.1.1.1 | Medical condition in easily understood language |
Patients at cardiovascular risk and statin intolerance due to statin-associated muscle symptoms (SAMS) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
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 |
: To assess the change in arterial wall inflammation, measured with 18F-FDG PET/CT scan, in patients at increased CV-risk and statin-associated muscle symptoms precluding statin use, before versus after 12 week therapy with Alirocumab 150mg once per 2 weeks subcutaneously. |
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E.2.2 | Secondary objectives of the trial |
1. To determine hematopoietic activity in bone marrow measured by 18F-FDG PET/CT before and after 12 weeks of Alirocumab 150mg once per 2 weeks subcutaneously. 2. To correlate the activity of arterial wall inflammation and bone marrow measured by 18F-FDG PET/CT with differences in innate immune cell phenotype before and after 12 weeks of Alirocumab 150mg once per 2 weeks subcutaneously.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
In order to be eligible to participate in this study, a subject must meet all of the following criteria: • Increased CV-risk o Clinical diagnosis of Familial Hypercholesterolemia, OR o Previous CV-event, OR o Imaging (CT, MRI, Angiography) compatible with atherosclerotic disease, OR o (very) high CV risk estimated by risk-engines (Framingham, Score, Procam) • Aged 50 years or older • Statin-associated Muscle symptoms (SAMS) for at least 3 different statins, precluding statin use • LDL-C > 100 mg/dL
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E.4 | Principal exclusion criteria |
A potential subject who meets any of the following criteria will be excluded from participation in this study: • Previous CV-event within 3 months prior to study screening visit • Malignant disease in past five years or any medical condition that could interfere with the conduct of the study in the opinion of the investigator. • Use of any dose of any statin • Chronic or recent (<1 month) infections and/or clinical signs of acute infection and/or CRP>10 mg/L • Auto-immune diseases • Use of chronic immunosuppressant or antibiotics in the last 6 weeks • Standard contra-indications to 18F-FDG PET/CT based on physicians experience and current practices • Inability or unwillingness to comply with the protocol requirements, or deemed by investigator to be unfit for the study. • Participation in a scientific study with radiation exposure in the year prior to inclusion.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the change in 18F-FDG target-to-background ratio (TBR) following 12 weeks of PCSK-9 inhibition. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
before and after 3 months of treatment with PCSK9 inhibition or placebo |
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E.5.2 | Secondary end point(s) |
The secondary endpoints are the difference in hematopoietic 18F-FDG activity in bone marrow before and after PCSK-9 inhibition and to evaluate whether there is a correlation between 18F-FDG PET activity in arterial wall and hematopoietic organs (i.e. bone marrow) and circulating immune cell phenotype including but not limited to monocytes. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
before and after 3 months of treatment with PCSK9 inhibition or placebo |
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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 | No |
E.6.5 | Efficacy | No |
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 | 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 | 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) | Yes |
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 | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |