Primary: long-term safety and efficacy of SAR236553 in high risk patients with an insufficiently controlled hypercholestolemia despite treatment with existing lipid modifying drugs.Secondary objectives: effect on individual lipids, development of…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
hypercholesterolemie
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Percent change from baseline in LDL-C at week 24. Adverse events.
Secondary outcome
E.g. % change from baseline in LDL-C at week 12, % patienst meeting the target
LDL-C value bereikt in week 24, development of antibodies, PK parameters.
Background summary
It is known that insufficiently or not controlled hypercholesterolemia leads to
and increased risk of cardiovascular disease. Statins are the cornerstone of
the drug treatment of hypercholesterolemia.
SAR236553 is a fully human monoclonal antibody that binds PCSK9 and blocks its
effect on the LDL receptors located at the surface of liver cells; LDL
receptors are in charge of the removal of LDL-cholesterol (bad cholesterol)
from the blood. The substance PCSK9 is secreted into the blood and directly
binds to the LDL receptors promoting their breakdown. The increased breakdown
of LDL receptors leads to a reduced LDL-cholesterol removal from the blood, and
therefore higher LDL-cholesterol circulating levels. Therefore, blocking PCSK9
binding to the LDL receptors through the use of SAR236553 can potentially
benefit patients suffering from hypercholesterolemia by decreasing the blood
LDL-cholesterol levels.
In this study long-term safety and efficacy of SAR236553 will be investigated
in high risk patients with an insufficiently controlled hypercholestolemia
despite treatment with existing lipid modifying drugs.
Study objective
Primary: long-term safety and efficacy of SAR236553 in high risk patients with
an insufficiently controlled hypercholestolemia despite treatment with existing
lipid modifying drugs.
Secondary objectives: effect on individual lipids, development of
anti-SAR236553 antibodies, PK.
Study design
Multicenter randomized double-blind phase III parallel-group placebo-controlled
study.
Randomisation (2:1) to:
* SAR236553 150 mg s.c. every 2 weeks
* Placebo.
Stable background treatment with existing lipid-lowering therapy.
Screening period of max. 3 weeks. Treatment period 18 months. Follow-up 8 weeks.
Independent DSMB.
An interim analysis when 600 patients have concluded the 18 months treatment
period..
Approx. 2100 patients.
Intervention
Treatment with SAR236553 or placebo.
Study burden and risks
Risk: Adverse effects of study medication.
Burden: Max. study duration approx. 20 months. 13 visits (11 fasting). Duration
0,5-3 h.
SC injection (1 ml) every 2 weeks.
Physical examination 6x.
Colour vison test (to exclude optic nerve problems as an adeverse event) 4x.
Blood tests 11x, 395 ml in total.
5x10 ml blood for future testing in relation to the study medication.
Optional pharmacogenetic blood tests (12 ml).
Pregnancy test (if relevant) 7x.
ECG 5x.
Questionnaire QoL.
Dietary councelling.
Avenue Marcel Thiry 77
Brussel 1200
BE
Avenue Marcel Thiry 77
Brussel 1200
BE
Listed location countries
Age
Inclusion criteria
Either A or B below and who are not adequately controlled with their lipid modifying therapy: A) Patients with heterozygous familial hypercholesterolemia (heFH) with or without established coronary heart disease (CHD) or CHD risk equivalents
OR
B) Patients with hypercholesterolemia together with established CHD or CHD risk equivalents.
See protocol for more details
Exclusion criteria
* Age < 18 years.
* LDL-C <1.81 mmol/L.
* Statin that is not simvastatin, atorvastatin, or rusovastatin
* simvastatin, atorvastatin, or rusovastatin is not taken dialy or not taken at a registered dose.
* Daily doses above atorvastatin 80 mg, rosuvastatin 40 mg or simvastatin 40 mg (except for patients on simvastatin 80 mg for more than one year, who are eligible).
* Fasting serum TG >4.52 mmol/L)
* Use of fibrates other than fenofibrate within 6 weeks
* Known history of active optic nerve disease
* Pregnancy, inadequate anticonception, breast feeding
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 | clinicaltrials.gov; registratienummer n.n.b. |
| EudraCT | EUCTR2011-002806-59-NL |
| CCMO | NL39559.018.12 |