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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057100 |
E.1.2 | Term | Homozygous familial hypercholesterolaemia |
E.1.2 | System Organ Class | 100000004850 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057099 |
E.1.2 | Term | Heterozygous familial hypercholesterolaemia |
E.1.2 | System Organ Class | 100000004850 |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To describe the safety and tolerability of 80 weeks of SC evolocumab when added to standard of care in pediatric subjects 10 to 17 years of age with HeFH or HoFH. |
|
E.2.2 | Secondary objectives of the trial |
To describe percent change and change from baseline in LDL-C, and on percent change from baseline in non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), total cholesterol/HDL-C ratio, and ApoB/Apolipoprotein A-1 (ApoA1) ratio. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects with HeFH:
-Completed Study 20120123 while still on assigned investigational product.
Subjects with HoFH:
-Male or female, ≥ 10 to ≤ 17 years of age at time of enrollment
-Diagnosis of HoFH by genetic confirmation or a clinical diagnosis based on a
history of an untreated LDL cholesterol concentration > 500 mg/dL (13 mmol/L)
together with either xanthoma before 10 years of age or evidence of
heterozygous familial hypercholesterolemia in both parents.
All subjects:
- Subject must be on a low-fat diet and receiving background lipid-lowering therapy
-Lipid-lowering therapy, including statin dose, must be unchanged for ≥ 4 weeks
prior to LDL-C screening; fibrates must be stable for at least 6 weeks prior to
screening. |
|
E.4 | Principal exclusion criteria |
Subjects with HoFH:
- estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m2; CK > 3x ULN; AST or ALT > 3x ULN; (all screening by central laboratory);
- known active infection or major hematologic, renal, metabolic, gastrointestinal or endocrine dysfunction;
- subject has taken a cholesterylester transfer protein (CETP) inhibitor in the last 12 months, or mipomersen or lomitapide in the last 5 months prior to LDL-C screening, or has received any therapy to inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9) within 12 weeks prior to screening;
- subject has a history or evidence of any other clinically significant disorder, condition or disease, or planned or expected procedure that, in the opinion of the Investigator or Amgen physician, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
The following are major exclusion criteria for all subjects:
- subjects cannot be receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study;
- female subjects of childbearing potential cannot be pregnant or breast feeding or planning to become pregnant or planning to breast feed and must be willing to use acceptable method(s) of effective birth control (may include true sexual abstinence) during treatment with evolocumab and for an additional 15 weeks after the end of treatment with evolocumab. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Subject incidence of treatment emergent adverse events |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Screening, day 1, weeks 4, 12, 24, 36, 48, 60, 72 and 80. |
|
E.5.2 | Secondary end point(s) |
Percent change from baseline at week 80 in:
− LDL-C
− Non-HDL-C
− ApoB
− Total cholesterol/HDL-C ratio
− ApoB/ApoA1 ratio
• Change from baseline in LDL-C at week 80 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | 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 | Yes |
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 | 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 | 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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 |
Australia |
Austria |
Belgium |
Brazil |
Canada |
Colombia |
Czechia |
Germany |
Hungary |
Italy |
Netherlands |
New Zealand |
Norway |
Poland |
Portugal |
Russian Federation |
Slovenia |
South Africa |
Spain |
Turkey |
United Kingdom |
|
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 | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 2 |