E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
Elevated levels of ’bad’ cholesterol |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020603 |
E.1.2 | Term | Hypercholesterolaemia |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
|
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 evaluate the effect of evolocumab on arterial wall inflammation, as measured by percent change from baseline in target-to-background ratio of an index vessel by FDG-PET/CT at week 16 in subjects with baseline lipoprotein (a) [Lp(a)] ≥ 50 mg/dL and low density lipoprotein-cholesterol (LDL-C) ≥ 100 mg/dL |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the effect of evolocumab on
- Lp(a)
- LDL-C
- Apolipoprotein B (ApoB) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female, ≥ 50 years of age at the time of informed consent
- Subject with fasting Lp(a) ≥ 50 mg/dL at screening 1
- Subject with fasting LDL-C ≥ 100 mg/dL at screening 1
- For those subjects receiving lipid lowering therapy, lipid-lowering therapy, including statin dose, must be unchanged for ≥ 8 weeks prior to screening |
|
E.4 | Principal exclusion criteria |
- Known diagnosis of diabetes mellitus or screening fasting serum glucose ≥ 126 mg/dL or HbA1C ≥ 6.5%
- A history of homozygous familial hypercholesterolemia
- Recent cardiovascular event within 3 months prior to randomization, or planned cardiac surgery, PCI or carotid stenting, or planned major non-cardiac surgery during the course of the study period
- Currently undergoing lipid apheresis
- Known contraindications or limitations to FDG-PET/ CT
- Auto-immune disease/vasculitis, active inflammatory diseases, proven or suspected bacterial infections. Recent (< 1 month prior to screening) or ongoing serious infection requiring intravenous antibiotic therapy
- Recent (< 6 weeks prior to screening) or current treatment with medications that may have a significant effect on plaque inflammation as measured by plaque TBR, including: oral, rectal, or injectable corticosteroids or immunosuppressive medications
- Recent (< 6 weeks prior to screening) or current treatment with aspirin (> 325 mg/day) or NSAIDs (> 1000 mg/day)
- Known sensitivity to any of the active substances or excipients to be administered during dosing
- Subject has taken a cholesterol ester transfer protein inhibitor or mipomersen or lomitapide in the last 12 months prior to screening
- Known systemic disorders or any clinically significant medical condition that could interfere with the conduct of the study
- History of malignancy (except non-melanoma skin cancers, cervical in-situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma) within the last 5 years
- Subject has previously received evolocumab or any other therapy to inhibit PCSK9 |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Percent change from baseline in TBR within the MDS of the index vessel
(right carotid, left carotid, or thoracic aorta) by FDG-PET/CT |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
[2EP-1] Percent change in Lp(a)
[2EP-2] Percent change in LDL-C
[2EP-3] Percent change in ApoB |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
[2EP-1] Baseline, Day 1, Week 8, Week 16
[2EP-2] Baseline, Day 1, Week 8, Week 16
[2EP-3] Baseline, Day 1, Week 8, Week 16 |
|
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 | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | 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 | 6 |
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
|
|
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 | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |