Primary objective: To evaluate the efficacy of alirocumab, on low-density lipoprotein cholesterol (LDL-C) levels of treatment in children with homozygous familialhypercholesterolemia (hoFH) 8 to 17 years of age on top of background treatments.…
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 LDL-C from baseline to Week 12 in the intent-to-treat (ITT)
population, using all LDL-C values regardless of adherence to treatment (ITT
estimand).
Secondary outcome
- Percent change in LDL-C from baseline to Week 12 in the ITT population, using
all LDL-C values during the treatment period (on-treatment estimand).
- Percent change in LDL-C from baseline to Weeks 24 and 48 (ITT and
on-treatment estimands).
- Percent change in Apo B, non-HDL-C, total-C, Lp (a), HDL-C, fasting TG, and
Apo A-1 (pre-apheresis, if applicable) from
baseline to Weeks 12, 24, and 48 (ITT and on-treatment estimands).
- Proportion of patients with *15% reduction in LDL-C at Weeks 12, 24, and 48
(ITT and on-treatment estimands).
- The absolute change in LDL-C from baseline to Weeks 12, 24, and 48 (ITT and
on-treatment estimands).
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 the liver cells resulting in lower levels of circulating LDL-C.
This study is designed to evaluate the efficacy, safety and pharmacokinetics
(PK) of alirocumab in the pediatric population (ages 8 to 17) with homozygous
familial hypercholesterolemia.
Study objective
Primary objective:
To evaluate the efficacy of alirocumab, on low-density lipoprotein cholesterol
(LDL-C) levels of treatment in children with homozygous
familialhypercholesterolemia (hoFH) 8 to 17 years of age on top of background
treatments.
Secondary objectives:
-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.
Study design
Phase 3, open label, 75 or 150 mg/ml (depending on body weight)
Intervention
Alirocumab 75 or 150 mg/ml SC Q2W
Study burden and risks
Risks and burdens related to blood collection, study procedures and possible
adverse events.
Paasheuvelweg 25
Amsterdam 1105BP
NL
Paasheuvelweg 25
Amsterdam 1105BP
NL
Listed location countries
Age
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.
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.
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 | 2017-002297-39 |
| EudraCT | EUCTR2017-002297-39-NL |
| CCMO | NL65086.018.18 |