A Randomized, Double-blind, Placebo Controlled Study to Assess Efficacy, Safety and Tolerability of LCQ908 in Subjects With Familial Chylomicronemia Syndrome
Condition: Familial Chylomicronemia Syndrome (FCS)
MeSH terms: Hyperlipoproteinemia Type I; Syndrome
Intervention: LCQ908; Placebo
Intervention description: LCQ908 10 mg, LCQ908 20 mg, LCQ908 40 mg; LCQ908 10 mg, LCQ908 20 mg, LCQ908 40 mg
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 45.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Hyperlipoproteinemia (HLP Type I); Fasting Triglycerides

Summary:

      The purpose of this study is to determine whether LCQ908 is effective and safe in lowering
      triglycerides in subjects with Familial Chylomicronemia Syndrome (FCS) (Hyperlipoproteinemia
      [HLP] type I). Data from this study will be used to support a registration submission of
      LCQ908 20 mg and 40 mg as treatment of chylomicronemia in subjects with FCS (HLP Type 1).
    

Eligibility criteria:

        Key Inclusion Criteria:

          1. Written informed consent given before any assessment was performed for Period I.

          2. Male and female patients ages at least 18 years of age.

          3. Fasting triglyceride ≥ 8.4 mmol/L (750 mg/dL) at Screening.

          4. An established diagnosis of FCS (HLP Type I) confirmed through ultracentrifugation or
             by documented medical history of a fasting triglyceride ≥ 8.4 mmol/L (750 mg/dL) and
             by documentation of any of the following at Screening or during the Screening Period:

               -  Confirmed homozygote or compound heterozygote for known loss-of-function
                  mutations in Type I-causing genes (such as LPL, apo C II, GPIHBP1, or LMF1)

               -  Post heparin plasma LPL activity of ≤ 20% of normal

               -  Confirmed presence of LPL inactivating antibodies

          5. History of pancreatitis.

        Key Exclusion Criteria:

          1. Current pancreatitis, pancreatitis was required to be inactive for at least 1 week
             prior to the screening Visit.

          2. Treatment with fish oil preparations within 4 weeks prior to randomization.

          3. Treatment with bile acid binding resins (i.e., colesevelam, etc.) within 4 weeks prior
             to randomization.

          4. Treatment with fibrates within 4 weeks prior to randomization.

          5. Glybera [alipogene tiparvovec (AAV1-LPLS447X)] gene therapy exposure within the two
             years prior to screening.

          6. History of malignancy of any organ system (other than localized basal cell carcinoma
             of the skin), treated or untreated, within the past 5 years, regardless of whether
             there is evidence of local recurrence or metastases.

          7. Any surgical or medical conditions, acute or unstable chronic disease which may, based
             on the investigator's opinion, jeopardize the patient in case of participation in the
             study or might significantly alter the absorption, distribution, metabolism or
             excretion of the study drug.

          8. History of drug or alcohol abuse within the 12 months prior to randomization or
             evidence of such abuse at screening.

          9. Evidence of liver disease or liver injury as indicated by abnormal liver function
             tests such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT), or
             serum bilirubin.

         10. Estimated glomerular filtration rate (eGFR) <30mL/min/1.73m2 or history of chronic
             renal disease.

         11. Participation in any clinical investigation within four (4) weeks prior to initial
             dosing or longer if required by local regulations, or any other limitation of
             participation based on local regulations.

         12. History of hypersensitivity to any of the study drugs or to drugs of similar chemical
             classes.

         13. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a
             female after conception and until the termination of gestation, confirmed by a
             positive HCG laboratory test.

         14. Women of child-bearing potential, defined as all women physiologically capable of
             becoming pregnant, unless they are using highly effective methods of contraception
             during dosing and for 100 days after discontinuation of investigational study drug.