Primary goal: To evaluate the efficacy of alirocumab administered every 2 weeks (Q2W) versus placebo after 24 weeks of double-blind (DB) treatment on low-density lipoprotein cholesterol (LDL-C) levels in children with heterozygous familial…
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 low-density lipoprotein cholesterol (LDL-C) from baseline to
Week 24
Secondary outcome
- Percent change in LDL-C
- Percent change in Apo B
- Percent change in non-HDL-C
- Percent change in Total-C
- Proportion of patients with LDL-C level < 3.37 mmol/L
- Proportion of patients with LDL-C level < 2.84 mmol/L
- Percent change in lipoprotein (a)
- Percent change in HDL-C
- Percent change in fasting triglycerides (TG)
- Percent change in apolipoprotein A1 (Apo A-1)
- Number of patients with adverse events
- Maturing cognition (Cogstate Battery Test)
Background summary
Familial hypercholesterolemia (FH) is a hereditary disorder of lipid
metabolism, characterized by severely elevated levels of low-density
lipoprotein (LDL-c) leading to early onset of atherosclerosis and
cardiovascular disease (CVD). It has been shown that these complications occur
already in early childhood. To be treated effectively, prevention must begin
decades prior to the onset of symptoms.
Alirocumab is an antibody that targets a specific protein (PCSK9) that reduces
the number of LDL receptors on liver cells which remove LDL from the blood
circulation. PCSK9 inhibition results in more receptors being present on the
surface of liver cells resulting in lower levels of circulating LDL-C.
This study is designed to evaluate the efficacy and safety of alirocumab in the
pediatric population (ages 8 to 17) with heterozygous familial
hypercholesterolemia.
Study objective
Primary goal:
To evaluate the efficacy of alirocumab administered every 2 weeks (Q2W) versus
placebo after 24 weeks of double-blind (DB) treatment on low-density
lipoprotein cholesterol (LDL-C) levels in children with heterozygous familial
hypercholesterolemia 8 to 17 years of age on top of background treatment.
Secondary goals:
-To evaluate the efficacy of alirocumab versus placebo on low-density
lipoprotein cholesterol (LDL-C) levels.
-To evaluate the effects of alirocumab versus placebo on other lipid parameters.
-To evaluate the safety and tolerability of alirocumab in comparison with
placebo.
-To evaluate the efficacy, safety, and tolerability of alirocumab after open
label treatment.
-To evaluate the development of anti-alirocumab antibodies.
Study design
Phase 3, double-blind, placebo-controlled study, followed by open-label
treatment.
Intervention
Alirocumab 40, 75 or 150 mg/ml or placebo SC Q2W
Alirocumab 75, 150 or 300 mg/ml or placebo SC Q4W
Study burden and risks
Risk and burdens related to blood collection, study procedures and possible
adverse events.
Paasheuvelweg 25
Amsterdam 1105 BP
NL
Paasheuvelweg 25
Amsterdam 1105 BP
NL
Listed location countries
Age
Inclusion criteria
-Children and adolescent male and female patients aged 8 to 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 except for patients
who have previously participated in the DFI14223 study., -A signed informed
consent indicating parental permission with or without patient assent.
Exclusion criteria
-Patient with body weight less than 25 kg., -Patients aged of 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 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., -Patients with
uncontrolled type 1 or type 2 diabetes mellitus., -Patients with known
uncontrolled thyroid disease., -Patients with uncontrolled 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.
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 |
|---|---|
| Other | 2017-001903-60 |
| EudraCT | EUCTR2017-001903-60-NL |
| CCMO | NL65553.018.18 |