Familial Chylomicronemia Syndrome (FCS)
Conditions
Interventions
Eligible patients will be randomized 1:1 (ISIS 304801:placebo) to receive for
52 weeks ISIS 304801 or placebo. All patients receive 1x per week ISIS 304801
300 mg or a corresponding volume of placeb
Sponsors
ISIS Pharmaceuticals
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Must give written informed consent to participate in the study (signed and dated) and any authorizations required by law 2. Age >= 18 years at time of informed consent 3. History of chylomicronemia as evidenced by documentation of lactescent serum (a creamy top layer after ultracentrifugation of a fasting blood sample) or documentation of fasting TG measurement >= 880 mg/dL (10 mmol/L) 4. A diagnosis of Familial Chylomicronemia Syndrome (Type 1 Hyperlipoproteinemia) by documentation of at least one of the following: a. Confirmed homozygote, compound heterozygote or double heterozygote for known loss-of-function mutations in Type 1-causing genes (such as LPL, apoCII, GPIHBP1, or LMF1) b. Post heparin plasma LPL activity of = 750 mg/dL (8.4 mmol/L) at Screening. If the fasting TG 55 years of age or, in females
Exclusion criteria
Exclusion criteria: 1. Diabetes mellitus with any of the following: a. Newly diagnosed within 12 weeks of screening b. HbA1c >= 9.0% at screening c. Recent change in anti-diabetic pharmacotherapy (change in dosage or addition of new medication within 12 weeks of screening [with the exception of ± 10 units of insulin]) d. Anticipated need to change dose or type of medication during the treatment period of the Study [with the exception of ± 10 units of insulin] e. Current use of GLP-1 agonists 2. Severe hypertriglyceridemia other than due to familial chylomicronemia syndrome 3. Active pancreatitis within 4 weeks prior to screening 4. History within 6 months of screening of acute or unstable cardiac ischemia (myocardial infarction, acute coronary syndrome, new onset angina), stroke, transient ischemic attack or unstable congestive cardiac failure requiring a change in medication or major surgery within 3 months of screening 5. Any of the following laboratory values at Screening a. Hepatic: • Total bilirubin > upper limit of normal (ULN), unless prior diagnosis and documentation of Gilbert*s syndrome in which case total bilirubin must be 2.0 x ULN • AST > 2.0 x ULN b. Renal: • Persistently positive (2 out of 3 consecutive tests >= 1+) for protein on urine dipstick. In the event of a positive test eligibility may be confirmed by a quantitative total urine protein measurement of = trace positive) for blood on urine dipstick. In the event of a positive test eligibility may be confirmed with urine microscopy showing ULN at Screening d. LDL-C > 130 mg/dL at Screening e. Any other laboratory abnormalities which, in the opinion of the Investigator or the Sponsor, would make the patient unsuitable for inclusion 6. Uncontrolled hypertension (BP > 160/100 mm Hg) 7. History of bleeding diathesis or coagulopathy or clinically significant abnormality in coagulation parameters at Screening 8. History of heart failure with NYHA greater than Class II 9. Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to Study Day 1 10. Known history of or positive test for human immunodeficiency virus (HIV), hepatitis C or chronic hepatitis B 11. Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated 12. Treatment with another investigational drug, biological agent, or device within one month of screening, or 5 half-lives of investigational agent, whichever is longer 13. Unwilling to comply with lifestyle requirements (Section 6.3) 14. Use of any of the following: a. Statins, omega-3 fatty acids (prescription and OTC), or fibrates unless on a stable dose for at least 3 months prior to screening and dose and regimen expected to remain constant during the treatment period. Patients taking OTC omega-3 fatty acids should make every effort to remain on the same brand throughout the study b. Nicotinic acid or derivatives of nicotinic acid within 4 weeks prior to screening c. Systemic corticosteroids or anabolic steroids within 6 weeks prior to screening unless app
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint is the % change in fasting TG from baseline as measured at the primary analysis time point. | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary endpoints include: • Postprandial TG change from baseline • Absolute change from baseline in fasting TG as measured at the primary analysis time point • Treatment response rate, where a patient with fasting plasma TG =40% reduction in fasting TG from baseline at the primary analysis time point is defined as a responder • Frequency and severity of patient reported abdominal pain during the treatment period • Composite of episodes of acute pancreatitis and patient reported abdominal pain during the treatment period • Change from baseline in hepatosplenomegaly as assessed by MRI | — |
Countries
Netherlands
Outcome results
None listed