E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Homozygous Familial Hypercholesterolemia |
|
E.1.1.1 | Medical condition in easily understood language |
Homozygous Familial Hypercholesterolemia |
|
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 | 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 efficacy of alirocumab administered every 2 weeks (Q2W), on low-density lipoprotein cholesterol (LDL-C) levels of treatment in children with homozygous familial hypercholesterolemia (hoFH) 8 to 17 years of age on top of background treatments. |
|
E.2.2 | Secondary objectives of the trial |
-To evaluate the efficacy of alirocumab after treatment on LDL-C levels.
-To evaluate the effects of alirocumab on other lipid parameters.
-To evaluate the safety and tolerability of alirocumab. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Patients genetically diagnosed with homozygous familial hypercholesterolemia (hoFH).
-Patients treated with optimal dose of statin +/- other lipid modifying therapies (LMTs), or non-statin LMTs if statin-intolerant at stable dose(s) for at least 4 weeks prior to screening lipid sample.
-A signed informed consent indicating parental permission with or without patient assent.
-For patients on apheresis, currently undergoing stable low-density lipoprotein (LDL) apheresis therapy prior to the screening and have initiated apheresis treatment for at least 6 months. |
|
E.4 | Principal exclusion criteria |
-Patients with low-density lipoprotein - cholesterol (LDL-C) less than 130 mg/dL (3.37 mmol/L) obtained during the screening period after the patient has been on stable apheresis procedure or lipid modifying therapy (LMT) (i.e., stable optimal dose of statin ± other stable LMTs, or stable non statin LMTs in statin-intolerant patients) treatment for at least 4 weeks.
-Patients with body weight less than 25 kg.
-Patients aged 8 to 9 years not at Tanner Stage 1 and patients aged of 10 to 17 years not at least at Tanner Stage 2 in their development.
-Patients with uncontrolled Type 1 or 2 diabetes mellitus.
-Patients with known uncontrolled thyroid disease.
-Patients with uncontrolled hypertension.
-Fasting triglycerides >350 mg/dL.
-Severe renal impairment (i.e., estimated glomerular filtration rate [eGFR] <30 mL/min/1.73m^2) at the screening visit.
-Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 x upper limit of normal (ULN).
-Creatine phosphokinase (CPK) >3 x ULN. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Percent change in LDL-C (pre-apheresis, if applicable) from baseline to Week 12, using all LDL-C values (pre-apheresis, if applicable) regardless of adherence to treatment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1. Percent change in LDL-C (pre-apheresis, if applicable) from baseline to Week 12, using all LDL-C values during the treatment period.
2. Percent change in LDL-C (pre-apheresis, if applicable).
3. Percent change in apolipoprotein B (Apo B) (pre-apheresis, if applicable).
4. Percent change in non-high density lipoprotein cholesterol (non-HDL-C) (pre-apheresis, if applicable).
5. Percent change in total cholesterol (total-C) (pre-apheresis, if applicable).
6. Percent change in lipoprotein (a) (Lp(a)) (pre-apheresis, if applicable).
7. Percent change in high-density lipoprotein cholesterol (HDL-C) (pre-apheresis, if applicable).
8. Percent change in fasting triglycerides (TG) (pre-apheresis, if applicable).
9. Percent change in apolipoprotein A1 (Apo A-1) (pre-apheresis, if applicable).
10. Proportion of patients with ≥15% reduction in LDL-C (pre-apheresis, if applicable).
11. Absolute change in LDL-C.
12. Number of patients with adverse events.
13. Tanner stage : the Tanner stage will be measured to assess stages of pubertal development. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. From baseline to Week 12
2. From baseline to Weeks 24 and 48
3. From baseline to Week 12, to Week 24, and to Week 48
4. From baseline to Week 12, to Week 24, and to Week 48
5. From baseline to Week 12, to Week 24, and to Week 48
6. From baseline to Week 12, to Week 24, and to Week 48
7. From baseline to Week 12, to Week 24, and to Week 48
8. From baseline to Week 12, to Week 24, and to Week 48
9. From baseline to Week 12, to Week 24, and to Week 48
10. From baseline to Weeks 12, 24 and 48
11. From baseline to Weeks 12, 24 and 48
12. Up to Week 62
13. At Weeks 24, 24, and 48 |
|
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 | No |
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 |
|
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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 | No |
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.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 |
Austria |
Brazil |
Bulgaria |
Canada |
France |
Italy |
Mexico |
Netherlands |
Norway |
Russian Federation |
Slovenia |
Spain |
Taiwan |
Turkey |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |