Elevated LDL-cholesterol is a major risk factor for heart disease. In patients with heart disease LDL-cholesterol should be lowered to levels below 70 mg/dl to prevent progression of disease. In most patients life style modification together with lipid lowering drug therapy is sufficient to achieve this goal. In some patients with severe forms of hypercholesterolemia, this may not be sufficient to reach goals and regular lipid apheresis (a costly and time intensive form of therapy) may be performed. Mipomersen is a new drug (apoB antisense oligonucleotide) that can lower LDL-cholesterol even in the most severe forms of LDL-hypercholesterolemia by 25-47%. It is unknown whether and to what extent mipomersen can decrease LDL-cholesterol in patients treated with regular apheresis. Phase 1 of the study will test how 6 months of weekly therapy with mipomersen affects LDL-cholesterol in patients with severe LDL-hypercholesterolemia treated with regular apheresis. Phase 2 will test in how many patients this will result in a meaningful reduction of apheresis time, apheresis frequency or if apheresis can be stopped completely.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
17
mipomersen 200 mg subcutaneously every week for 37 weeks (phase 1: 26 weeks; phase 2: 11 weeks)
University Munich
Munich, Germany
Change in pre-apheresis LDL-cholesterol (phase 1 of the study)
pre-apheresis LDL-cholesterol concentration will be averaged from 3 subsequent aphereses (exactly 1 week apart) before initiation of mipomersen therapy and after 6 months of weekly apheresis therapy; apheresis conditions will not be changed.
Time frame: 6 months
Fraction of patients in whom apheresis conditions can be modified (phase 2 of the study)
In phase 2 of the study mipomersen will be given weekly. It will be evaluated in what fraction of patients this results in a decrease of apheresis time, apheresis frequency or stopping of apheresis.
Time frame: 3 months
change in other lipid parameters
a number of additional lipid parameters will be evaluated before and during mipomersen therapy
Time frame: 6 months
Number of participants with adverse events
Time frame: 9 months (phase 1 and 2 of the study)
Plasma concentrations of mipomersen
pharmacokinetic sampling will be obtained following mipomersen administration at different time points during the study.
Time frame: 4 days after injection
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