The objective of the study is to assess the efficacy, tolerability and safety of SAR236553/Alirocumab when administered during 1.5years in patients with heterozygote familial hypercholesterolemia, who despite of lipid lowering therapy still have…
ID
Source
Brief title
Condition
- Metabolic and nutritional disorders congenital
- Lipid metabolism disorders
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by
SAR236553/Alirocumab as add-on therapy to stable maximally tolerated daily
statin therapy with or without other lipid-modifying therapy (LMT) in
comparison with placebo after 24 weeks of treatment in patients with
heterozygous familial hypercholesterolemia (heFH).
Secondary outcome
- To evaluate the effect of SAR236553/Alirocumab 75 mg in comparison with
placebo on LDL-C after 12 weeks of treatment.
- To evaluate the effect of SAR236553/Alirocumab on other lipid parameters (ie,
apolipoprotein B (Apo B), non-high-density lipoprotein cholesterol (non-HDL-C),
total cholesterol (total-C), lipoprotein (a) (Lp (a)), high-density lipoprotein
cholesterol (HDL-C), triglyceride (TG) levels, apolipoprotein A-1 (Apo A-1)
levels.
- To evaluate the long-term effect of SAR236553/Alirocumab on LDL-C.
- To evaluate the safety and tolerability of SAR236553/Alirocumab.
- To evaluate the development of anti-SAR236553/Alirocumab antibodies.
- To evaluate the pharmacokinetics (PK) of SAR236553/Alirocumab.
Background summary
The study will include patients with heterozygous familial hypercholesterolemia
(heFH) with or without a history of MI or ischemic stroke. Familial
hypercholesterolemia (FH) is an inherited disorder of lipid metabolism that
predisposes a person to premature severe cardiovascular disease (CVD). Familial
hypercholesterolemia has a high prevalence in Caucasian populations, were
estimated 1 in 500 individuals are affected.
In the heterozygous form of FH, the cumulative risk of experiencing a coronary
event by the age of 60 years without effective treament is at least 50% in men
and approximately 30% in women.
In 4 observational studies, statin therapy was shown to reduce the risk of CVD
by 50% to 80% in patients with FH. Unfortunately, even after treatment, the
risk in heFH can still be almost 2-fold higher than the general population. In
addition only a small fraction of treated heFH patients are able to reach
recommended levels of LDL-C. Thus, the need for more intensive treatment in
heFH patients is clear.
SAR236553/Alirocumab is a fully human monoclonal antibody that binds Propotein
Convertase Subtilisin Kexin type 9 (PCSK9).
PCSK9 which is highly expressed in the liver, is involved in regulating the
levels of Low-density lipoportein receptor (LDL-R) protein. Once secreted into
plasma, PCSK9 binds to the LDL-R and promotes its degeneration, which leads to
reduced LDL-C removal or higher LDL-C circulating levels.
Therefor blocking PCSK9 can potentially benefit patients by decreasing their
plasma LDL-C levels. In addition, PCSK9 messenger ribonucleic acid (mRNA) and
protein levels are increased in response to statins, potentially attenuating
their cholesterol-lowering effect.
Study objective
The objective of the study is to assess the efficacy, tolerability and safety
of SAR236553/Alirocumab when administered during 1.5years in patients with
heterozygote familial hypercholesterolemia, who despite of lipid lowering
therapy still have high cholestrol
Study design
Randomized double blind, placebo contrtoled, mutlicenter study with parallel
groups. Gerandomiseerd, dubbelblind, placebogecontroleerd, multicenter,
multinationale studie met parallelle groepen.
Randomization 2:1 to treatment (every 2 weeks s.c. injections) with
1. SAR236553/Alirocumab
2. placebo,
Stratified according to prior history of myocardial infarction (MI) or
ischemic stroke [Yes/No], statin treatment, and geographic region.
After randomization, patients.
Continue their maximal tolerated statins treattmnet with or without lipid
modifying treatement
Study duration +/- 18months
After completion of the 18 month double-blind treatment period, patients may be
offered to consent for another study (open-label extension study). Patients who
consent to participate in the open-label extension study will not undergo the
follow-up period.
Independent DSM
Intervention
Biweekly subcutenous injections with study drug/placebo
Study burden and risks
Riscs: adverse events of the study drug
Burden:
- 12 study visits and one follow-up visit in 18months. Patients need to come
fasted to the visits
- 39 subcutanous injections, by the patient or relative. Training is foreseen
and a diary needs to be completed for the administration
- Physical examininations: 4-5x
- Vital functions at every study visit
- Blooddraws (ca 30ms/draw) 12x
- Pregancy test (if relevant) 9x
- ECG 4x
- Questionnaire (Quality of life) 6x
- Optional pharmcokinetics ca. 12ml blood, 6x
Avenue Pierre Brossolette 1
Chilly Mazarin 91385
FR
Avenue Pierre Brossolette 1
Chilly Mazarin 91385
FR
Listed location countries
Age
Inclusion criteria
Patients with heterozygous familial hypercholesterolemia who are not adequately controlled with their lipid-modifying therapy.
Exclusion criteria
- Age < 18 years
- Patient without diagnosis of heFH made either by genotyping or by clinical criteria.
- LDL-C <70 mg/dL (<1.81 mmol/L) at the screening visit (Week-2) and patient with history of documented cardiovascular disease.
- LDL-C <100 mg/dL (<2.59 mmol/L) at the screening visit (Week-2) and patient without history of documented cardiovascular disease.
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 | EUCTR2011-005109-56-NL |
| Other | IND NUMMER 105574 |
| CCMO | NL41300.018.12 |