Effect of Mipomersen on LDL-Cholesterol Levels in Patients Treated by Regular Apheresis

NCT ID: NCT01598948

Last Updated: 2015-09-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-31
• Study Completion Date: 2015-06-30

Brief Summary

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.

Conditions

Atherosclerosis; LDL-hypercholesterolemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Mipomersen

Patients randomized to this arm will receive mipomersen 200 mg weekly

Group Type: EXPERIMENTAL

mipomersen

Intervention Type: DRUG

mipomersen 200 mg subcutaneously every week for 37 weeks (phase 1: 26 weeks; phase 2: 11 weeks)

Control

patients randomized to this arm will receive no additional drug

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

mipomersen

mipomersen 200 mg subcutaneously every week for 37 weeks (phase 1: 26 weeks; phase 2: 11 weeks)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• The patient fulfils German criteria for regular LDL-apheresis
• Regular (weekly) LDL-apheresis >/= 3 months
• The patient has fasting pre-apheresis LDL-C >/= 130 mg/dL at screening.
• The patient is receiving a stable, maximally tolerated, lipid-lowering regimen
• The patient has a body mass index (BMI) </= 40 kg/m2 with weight stable (± 4 kg) for > 6 weeks prior to screening.
• Written informed consent of the patient

Exclusion Criteria

• The patient has experienced MI, percutaneous transluminal coronary intervention (PTCI), CABG, cerebrovascular accident, unstable angina, or acute coronary syndrome within 12 weeks of screening.
• The patient has insulin-dependent diabetes mellitus (Type 1), or if Type 2 diabetes, HbA1c > 8% at screening.
• The patient has New York Heart Association (NYHA) functional classification III or IV heart failure.
• The patient has systolic blood pressure > 160 mm Hg or diastolic blood pressure > 95 mm Hg at screening (despite antihypertensive medication/therapy).
• The patient has an active infection requiring systemic antiviral or antimicrobial therapy unless treatment expected to be completed by day 1.
• The patient has a positive test for HIV or hepatitis B or C at screening.
• The patient has any uncontrolled condition that may predispose to secondary hyperlipidemia such as uncontrolled hypothyroidism.
• The patient has had a malignancy within 5 years, except for basal or squamous cell carcinoma of the skin that has been adequately treated.
• The patient has clinically significant hepatic (e.g. History of confirmed non-alcoholic steatohepatitis NASH) or renal disease or Gilbert's syndrome.
• The patient has previously received mipomersen treatment.
• The patient is on chronic systemic corticosteroids or anabolic agents except for replacement therapy.
• The patient has received treatment with another investigational drug, biological agent, or device within 4 weeks of screening or 5 half-lives of the study agent, whichever is longer.
• The patient has a current or a recent history of drug or alcohol abuse, or unwillingness to limit alcohol consumption to within moderate limits (maximum 20 g alcohol per day and 80 g alcohol per week for males; maximum 10 g alcohol per day and 40 g alcohol per week for females).
• Patient not able to give consent.
• Patient without legal capacity who is unable to understand the nature, scope, significance and consequences of this clinical trial.
• Known history of hypersensitivity to the investigational drug or to drugs with a similar chemical structure
• Simultaneous participation in another clinical trial or participation in any clinical trial involving administration of an investigational medicinal product within 30 days prior to the beginning of the clinical trial.
• Patient with a physical or psychiatric condition which at the investigator's discretion may put the patient at risk, may confound the trial results, or may interfere with the patient's participation in this clinical trial
• Known or persistent abuse of medication, drugs or alcohol

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ludwig-Maximilians - University of Munich

OTHER

Sponsor Role: lead

Responsible Party

Klaus Parhofer

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University Munich

Munich, , Germany

Countries

Germany

Other Identifiers

MICA

Identifier Type: -

Identifier Source: org_study_id