Primary objective: 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…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
familiaire hypercholesterolemie
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Percent change in calculated LDL-C
Secondary outcome
- Absolute change in calculated LDL-C
- Percentage of participants achieving a calculated LDL-C level lower than 130
mg/dL (3.37 mmol/L)
- Percentage of participants achieving a calculated LDL-C level lower than 110
mg/dL (2.84 mmol/L)
- Percent change in Apolipoprotein B (Apo B)
- Percent change in non-high density lipoprotein cholesterol (non-HDL-C)
- Percent change in Total-C
- Percent change in Lipoprotein (a) (Lp[a])
- Percent change in triglycerides (TG)
- Percent change in HDL-C
- Percent change in Apo A-1
- Absolute change in Apo B
- Absolute change in non-HDL-C
- Absolute change in Total-C
- Absolute change in Lp(a)
- Absolute change in TG
- Absolute change in HDL-C
- Absolute change in Apo A-1
- Absolute change in ratio Apo B/Apo A-1
Background summary
Familial hypercholesterolemia (FH) is an inherited disorder of lipid
metabolism, characterized by severely elevated levels of low-density
lipoprotein cholesterol (LDL-C) that lead to premature atherosclerosis and
cardiovascular disease (CVD). FH is the most clearly documented to have
important cardiovascular consequences beginning in childhood. To be effective
at preventing Coronary Heart Disease, prevention must begin decades prior to
the onset of symptoms.
Alirocumab is an antibody that targets a specific protein (PCSK9), which works
by reducing the number of receptors on the liver that remove LDL cholesterol
from the blood. By blocking PCSK9*s ability to work, more receptors are
available to get rid of LDL cholesterol from the blood and, as a result, lower
LDL cholesterol levels. Studies in adult patients have shown significant LDL
reductions.
This study is designed to evaluate the efficacy, safety and pharmacokinetics
(PK) of alirocumab in the pediatric population in order to support appropriate
dose selection of alirocumab for the Phase 3 pediatric study.
Study objective
Primary objective: 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.
Secondary objectives:
-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.
Study design
Phase 2, open label, ascending dose
Intervention
Cohort 1: Alirocumab SC Q2W
Cohort 2: Alirocumab SC Q2W
Cohort 3: Alirocumab SC Q4W
Cohort 4: Alirocumab SC Q4W
Study burden and risks
The most common side effects reported with alirocumab (occurring in at least 1%
of patients) include injection site reactions, itching and upper respiratory
symptoms.
Kampenringweg 45 E -
Gouda 2803 PE
NL
Kampenringweg 45 E -
Gouda 2803 PE
NL
Listed location countries
Age
Inclusion criteria
- Children and adolescent male and female patients aged of 8 to 17 years at the time of signed informed consent.
- Patients with a diagnosis of heterozygous familial hypercholesterolemia (he FH) through genotyping or clinical criteria.
- Patients treated with an optimal dose of statin with or without other LMT(s) or non-statin LMT(s) if statin intolerant at stable dose for at least 4 weeks prior to screening visit (Week -2).
- Patients with calculated LDL-C greater than or equal to 130 mg/dL (*3.37 mmol/L) at the screening visit (Week -2).
- Patients with body weight greater than or equal to 25 kg.
- Patients aged of 8 to 9 years to be at Tanner stage1 and patients aged 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, depending on capacity for understanding based on developmental maturity. In cases involving emancipated or mature minors with adequate decision-making capacity, or when otherwise
permitted by law, a signed informed consent directly from patients.
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) at the screening visit (Week -2).
- Severe renal impairment (ie, eGFR <30 mL/min/1.73 m2 at the screening visit [Week -2]).
- ALT or AST >2 x ULN (1 repeat lab is allowed).
- CPK >3 x ULN (1 repeat lab is allowed).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-003766-85-NL |
| Other | IND105574 |
| CCMO | NL57952.018.16 |