E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary Hypercholesterolemia |
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E.1.1.1 | Medical condition in easily understood language |
Primary Hypercholesterolemia |
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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 | PT |
E.1.2 | Classification code | 10077965 |
E.1.2 | Term | Primary hypercholesterolaemia |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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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 |
To demonstrate the superiority of inclisiran as monotherapy, compared with placebo, in reducing low-density lipoprotein cholesterol (LDL-C) as measured by percentage change from baseline to Day 150 & To demonstrate the superiority of inclisiran as monotherapy, compared with ezetimibe, in reducing LDL-C as measured by percentage change from baseline to Day 150 |
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E.2.2 | Secondary objectives of the trial |
To assess the efficacy of inclisiran as monotherapy, compared to ezetimibe and placebo, on absolute change in LDL-C, percentage change in Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC)/high -density lipoprotein cholesterol (HDL-C) ratio, apolipoprotein B (Apo B), Apo B/apolipoprotein A-1 (Apo A-1) ratio and lipoprotein (a) (Lp(a)) from baseline to Day 150. To assess the safety and tolerability of inclisiran as monotherapy, compared to placebo and ezetimibe. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Participants eligible for inclusion in this study must meet all of the following criteria at screening: 1. Signed informed consent must be obtained prior to participation in the study 2. Adults ≥ 18 to ≤ 75 years of age 3. Fasting LDL-C value of ≥ 100 mg/dL (equivalent to 2.59 mmol/L) but < 190 mg/dL (equivalent to 4.92 mmol/L) 4. Triglycerides ≤ 400 mg/dL (equivalent to 4.52 mmol/L) 5. With a 10-year ASCVD risk score of less than 7.5%, estimated using the pooled cohort equations (PCE) 6. Have not been on any lipid-lowering therapy within 90 days
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E.4 | Principal exclusion criteria |
Key Exclusion Criteria: ● Use of any LLT within 90 days of screening including statins, ezetimibe, bempedoic acid, psyllium preparations, fibrates, bile-acid sequestrants, PCSK9 monoclonal antibodies, red yeast rice, niacin > 200 mg/day, omega-3 fatty acids [docosahexaenoic acid (DHA) and/or eicosapentaenoic acid (EPA), with a total dose > 1000 mg/day], or any drug with unknown ingredients taken for the purpose of lipid-lowering, including over-the-counter or herbal therapies ● Use of systemic cyclosporine or tacrolimus, systemic steroids, vitamin A derivatives or retinal derivatives for the treatment of dermatologic conditions (vitamin A in a multivitamin preparation is permitted), or antiviral therapies (protease inhibitors or direct acting antivirals) within 30 days of screening ● Participants on medications that are known to induce changes in lipids and lipoproteins (including but not limited to anticoagulants, loop diuretics, thiazide diuretics, beta blockers, amiodarone, estrogens, selective estrogen receptor modulators, androgens, anabolic steroids, and anticonvulsants) unless they are on a stable dose of such medications for at least 30 days prior to screening and have no planned dose change or treatment discontinuation during the study duration ● History of ASCVD (including acute coronary syndrome, history of myocardial infarction, stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack, and peripheral artery disease including aortic aneurysm) ● Diabetes mellitus or fasting plasma glucose (FPG) at screening ≥ 7.0 mmol/L (equivalent to 126 mg/dL) or glycated hemoglobin (HbA1c) ≥ 6.5% (equivalent to 7.8 mmol/L or 140 mg/dL) ● Secondary hypercholesterolemia, e.g., hypothyroidism [thyroid stimulating hormone (TSH) above the upper limit of normal (ULN)] or nephrotic syndrome at screening |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage change in LDL-C from baseline to Day 150; Percentage change in LDL-C from baseline to Day 150 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Absolute change in LDL-C, percentage change in PCSK9, non-HDL-C, TC/HDL-C ratio, Apo B, Apo B/Apo A-1 ratio and Lp (a) from baseline to Day 150. Incidence of TEAEs and SAEs, safety laboratory values at each visit. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 | 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 | 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) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 12 |
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 |
Colombia |
Mexico |
United States |
Spain |
Germany |
Hungary |
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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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global last patient last visit |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | 21 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 20 |