E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 19.0 |
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 |
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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 evaluate the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C) levels after 8 weeks of treatment in heterozygous familial hypercholesterolemia (heFH) patients age of 8 to 17 years, with LDL-C ≥130 mg/dL (3.37 mmol/L) on optimal stable daily dose of statin therapy +/- other lipid modifying therapies (LMTs) or a stable dose of non-statin LMTs in case of intolerance to statins for at least 4 weeks prior to the screening period. |
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E.2.2 | Secondary objectives of the trial |
-To evaluate the safety and tolerability of alirocumab.
-To evaluate the pharmacokinetics profile of alirocumab.
-To evaluate the effects of alirocumab on other lipid parameters.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Children and adolescent male and female patients age of 8 to 17 years at the time of signed informed consent. For Russia only: Male and female patients aged ≥12 and ≤17 years at the time of signed informed consent.
-Patients with diagnosis of heterozygous familial hypercholesterolemia (heFH) through genotyping or clinical criteria.
-Patients treated with optimal dose of statin +/- other LMT(s) or non-statin LMT(s) if statin intolerant at stable dose for at least 4 weeks prior to screening lipid sampling
-Patients with calculated LDL-C greater than or equal to 130 mg/dL (≥3.37 mmol/L) at the screening visit
-Patients with body weight greater than or equal to 25kg.
-Patients age of 8 to 9 years to be at Tanner stage 1 and patients age of 10 to 17 years to be at least at Tanner stage 2 in their development.
-A signed informed consent indicating parental permission with or without patient assent.
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E.4 | Principal exclusion criteria |
-Patient with secondary hyperlipidemia.
-Diagnosis of homozygous familial hypercholesterolemia.
-Patient who has received lipid apheresis treatment within 2 months prior to the screening period, or has plans to receive it during the study.
-Known history of type 1 or type 2 diabetes mellitus.
-Known history of thyroid disease.
-Known history of hypertension.
-Fasting triglycerides >350 mg/dL (3.95 mmol/L).
-Severe renal impairment (ie, estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m^2.
-Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 x upper limit of normal (ULN).
-Creatinine phosphokinase (CPK) >3 x ULN.
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E.5 End points |
E.5.1 | Primary end point(s) |
Percent change in calculated LDL-C |
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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) |
a) Absolute change in calculated LDL-C
b) Percentage of participants achieving a calculated LDL-C level lower than 130 mg/dL (3.37 mmol/L)
c) Percentage of participants achieving a calculated LDL-C level lower than 110 mg/dL (2.84 mmol/L)
d) Percent change in Apolipoprotein B (Apo B)
e) Percent change in non-high density lipoprotein cholesterol (non HDL-C)
f) Percent change in Total-C
g) Percent change in Lipoprotein (a) (Lp[a])
h) Percent change in triglycerides (TG)
i) Percent change in HDL-C
l) Percent change in Apo A-1
m) Absolute change in Apo B
n) Absolute change in non-HDL-C
o) Absolute change in Total-C
p) Absolute change in Lp(a)
q) Absolute change in TG
r) Absolute change in HDL-C
s) Absolute change in Apo A-1
t) Absolute change in ratio Apo B/Apo A-1 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
a) From baseline to Week 8
b), c) : At week 8
d), e), f), g) h), I), l), m), n), o), p), q), r), s), t) : From baseline to Week 8
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 6 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
Australia |
Canada |
Czech Republic |
France |
Israel |
Netherlands |
Norway |
Russian Federation |
South Africa |
Spain |
Sweden |
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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
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E.8.9 Initial estimate of the duration of the trial |
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 | 6 |