E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hypercholesterolemia - The current trial will study children with Homozygous Familial Hypercholesterolemia (HoFH) |
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E.1.1.1 | Medical condition in easily understood language |
The current trial will study the fatty acid levels in children with a genetic disorder causing them to have high blood levels of fatty acids |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054380 |
E.1.2 | Term | Familial hypercholesterolemia |
E.1.2 | System Organ Class | 100000004850 |
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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 assess the efficacy of rosuvastatin 20 mg on low density lipoprotein cholesterol (LDL C), compared to placebo, after 6 weeks of treatment in pediatric patients with Homozygous Familial Hypercholesterolemia (HoFH) |
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E.2.2 | Secondary objectives of the trial |
To assess the efficacy of rosuvastatin 20 mg on LDL C, compared to placebo, after 6 weeks of treatment in pediatric patients with HoFH not treated with apheresis
To assess the efficacy of rosuvastatin 20 mg on lipid parameters other than LDL C, compared to placebo, after 6 weeks of treatment in pediatric patients with HoFH
To assess the longitudinal profile of LDL C during treatment with rosuvastatin 20 mg
To characterize the trough plasma exposure of rosuvastatin in pediatric patients with HoFH |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Prior to any study related procedures being performed, provision of written informed consent from a parent/both parents or guardian and statement of assent from the child or adolescent (if required by Institutional Review Board [IRB] or Independent Ethics Committee [EC] according to local regulations and guidelines). Communication between the Investigator, patient/guardian and child/adolescent to confirm understanding and required compliance with the requirements of the study;
2.Male and female children and adolescents (aged 6 to <18 years) with at least 1 of the following criteria:
Documentation of genetic testing confirming 2 mutated alleles of the LDL receptor gene locus; and/or
Documented untreated LDL C >500 mg/dL (12.9 mmol/L) and triglyceride (TG) <300 mg/dL (3.4 mmol/L) and at least 1 of the following criteria:
oTendinous and/or cutaneous xanthoma prior to 10 years of age; or
oDocumentation of HeFH in both parents by:
genetic and/or
clinical criteria;
3.Negative pregnancy test (b human chorionic gonadotropin analysis) prior to baseline in females of child bearing potential:
Female patients of child bearing potential must adhere to a pregnancy prevention method (abstinence, chemical, or mechanical) during the study and 3 months following the last dose;
Male patients should refrain from fathering a child (including sperm donation) during the study and up to 3 months following the last dose; and
4.Willing to follow all study procedures including adherence to dietary guidelines, study visits, fasting blood draws, and compliance with study treatment regimens.
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E.4 | Principal exclusion criteria |
1.History of statin inducted myopathy or serious hypersensitivity reaction to other HMG CoA reductase inhibitors (statins), including rosuvastatin, at Visit 1;
2.Fasting serum glucose of >9.99 mmol/L (180 mg/dL) or glycosylated hemoglobin >9% at Visit 1 or patients with a history of diabetic ketoacidosis within the past year;
3.Uncontrolled hypothyroidism defined as thyroid stimulating hormone (TSH) >1.5 times the upper limit of normal (ULN) at Visit 1 or patients whose thyroid replacement therapy was initiated or modified within the last 3 months prior to Visit 2;
4.Current active liver disease or hepatic dysfunction (except a confirmed diagnosis of Gilbert’s disease) as defined as elevations of 1.5 times the ULN for any age in any of the following liver function tests at Visit 1: ALT, AST, or bilirubin;
5.Definite or suspected personal history or family history of clinically significant adverse drug reactions (ADRs), or hypersensitivity to drugs with a similar chemical structure to rosuvastatin as well as other statins; |
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E.5 End points |
E.5.1 | Primary end point(s) |
"Describe efficacy in terms of low density lipoprotein cholesterol (LDL C) following 6 weeks rosuvastatin 20 mg or placebo treatment |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Samples taken Day 42 (week 6), Day 84 (week 12) |
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E.5.2 | Secondary end point(s) |
1 Describe efficacy in terms of low density lipoprotein cholesterol (LDL C) following 6 weeks rosuvastatin 20 mg or placebo treatment in patients not treated with Apheresis
2 Describe efficacy in terms of High density lipoprotein cholesterol (HDL C), total cholesterol (TC), triglyceride (TG), non-HDL C, LDL-C/HDL C, TC/HDL C, non-HDL-C/HDL C, apolipoprotein B (ApoB), ApoB/apolipoprotein A 1 (ApoA 1) and ApoA 1 following 6 weeks of treatment with rosuvastatin 20 mg or placebo
3 Describe the longitudinal profile of LDL C as a change in LDL C from end of placebo period to 6, 12, and 18 weeks of therapy with rosuvastatin 20 mg
4, Describe the pharmacokinetic profile in terms of trough concentrations
Safety
Adverse events, including:
• The frequency and severity of adverse events
• Rate of discontinuations due to adverse
events
• Abnormal serum and urine laboratory values,
ECGs, physical examinations, and vital signs
Assessments of growth, including height (linear
growth [cm and standard deviation (SD) score]),
weight, and secondary characteristics of sexual
maturation by Tanner stage performed at the
beginning of the lead-in phase (Visit 2) and at Visit 7 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 and 2: Samples taken Day 42 (week 6), Day 84 (week 12)
3. Samples taken Day 42 (week 6), Day 84 (week 12), Day 126 (week 18), Day 168 (week 24)
4. Samples taken Day 126 (week 18), Day 168 (week 24)
Safety
From screeing up to week 24
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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 | 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 | No |
E.8.1.6 | Cross over | Yes |
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
| 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 | 5 |
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 |
Belgium |
Czech Republic |
Hong Kong |
Israel |
Netherlands |
Norway |
South Africa |
Sweden |
Taiwan |
United Kingdom |
United States |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |