A Pilot Study to Assess the Efficacy and Safety of LCQ908 Alone and in Combination With Fenofibrate or Lovaza® in Patients With Severe Hypertriglyceridemia

Study Overview
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Brief Summary
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This study is to determine a dose response signal for LCQ908 monotherapy and to assess the efficacy and safety of adding LCQ908 to Lovaza or fenofibrate.

Official Title
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A Multicenter, Randomized, Active Comparator, Placebo Controlled, Double-blind Pilot Study to Assess the Efficacy and Safety of LCQ908 Alone and in Combination With Fenofibrate or Lovaza® in Patients With Severe Hypertriglyceridemia

Conditions
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Non Familial Chylocmicronemia Syndrome (Non-FCS)

Intervention / Treatment
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* Drug: LCQ908
* Drug: Fenofibrate
* Drug: Fish Oil
* Drug: Placebo of LCQ908
* Drug: Placebo of fenofibrate
* Drug: Placebo of fish oil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects ages >18 years of age, inclusive. History of plasma TG concentration ≥890 mg/dl (10 mmol/L) or history of lactescent plasma in the fasting state. Fasting TG ≥ 750 mg/dL (8.5 mmol/L) at day -7 or repeat of day -7 one week later for those failing to qualify initially and thought likely to qualify on repeat examination prior to randomization. Exclusion Criteria: Treatment with Omega-3 fatty acids or niacin or fibrates within 8 weeks of screening. Patients with confirmed Familial Chylomicronemia Syndrome (FCS) with hyperlipoproteinemia (HLP) Type-I diagnosis or known to be homozygotes or compound heterozygotes for mutations in HLP Type I-causing genes (such as LPL, apoCII, CPIHBP1, or LMF1) prior to screening. Pancreatitis within 3 months prior to screening. Uncontrolled type 2 diabetes (T2DM) (as defined by an HbA1c value of ≥8.0% at screening) BMI > 40 or history of bariatric surgery. Nephrotic syndrome, Type 1 diabetes, HIV, HCV or HBV positive. Estimated Glomerular Filtration Rate (eGFR) < 60 ml/min/1.73m2 Other protocol defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LCQ908 1<br>LCQ908 (Diacylglycerol acyltransferase inhibitor)once daily for 12 weeks | Drug: LCQ908<br> <br> Drug: Placebo of LCQ908<br>* Matching placebo of LCQ908<br>Drug: Placebo of fenofibrate<br>* Matching placebo of fenofibrate<br>Drug: Placebo of fish oil<br>* Matching placebo of fish oil capsule<br>|
| Experimental: LCQ908 2<br>LCQ908 once daily for 12 weeks | Drug: LCQ908<br> <br> Drug: Placebo of LCQ908<br>* Matching placebo of LCQ908<br>Drug: Placebo of fenofibrate<br>* Matching placebo of fenofibrate<br>Drug: Placebo of fish oil<br>* Matching placebo of fish oil capsule<br>|
| Experimental: LCQ908 3<br>LCQ908 once daily for 12 weeks | Drug: LCQ908<br> <br> Drug: Placebo of LCQ908<br>* Matching placebo of LCQ908<br>Drug: Placebo of fenofibrate<br>* Matching placebo of fenofibrate<br>Drug: Placebo of fish oil<br>* Matching placebo of fish oil capsule<br>|
| Active Comparator: Fenofibrate<br>Intervention Type: Drug Intervention Name: Fenofibrate | Drug: LCQ908<br> <br> Drug: Fenofibrate<br>* Fenofibrate once daily 12 weeks<br>Drug: Placebo of LCQ908<br>* Matching placebo of LCQ908<br>Drug: Placebo of fish oil<br>* Matching placebo of fish oil capsule<br>|
| Active Comparator: Fish Oil<br>Fish oil once daily for 12 weeks | Drug: LCQ908<br> <br> Drug: Fish Oil<br>* Fish Oil once daily for 12 weeks<br>* Other names: Lovaza®;Drug: Placebo of LCQ908<br>* Matching placebo of LCQ908<br>Drug: Placebo of fenofibrate<br>* Matching placebo of fenofibrate<br>|
| Placebo Comparator: Arm Label: Placebo<br>Intervention Type: other Intervention Name: other | Drug: Placebo of LCQ908<br>* Matching placebo of LCQ908<br>Drug: Placebo of fenofibrate<br>* Matching placebo of fenofibrate<br>Drug: Placebo of fish oil<br>* Matching placebo of fish oil capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in triglycerides (TG) relative to placebo at 6 weeks | The dose response signal of 3 dose regiments of LCQ908 in patients at risk for non-FCS chylomicronemia as was measured by change from baseline in triglycerides (TG) relative to placebo at 6 weeks. | Baseline, 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in triglycerides after adding LCQ908 to background therapy of fenofibrate or Fish Oil at 12 weeks |  | Baseline, 12 weeks | 
| Changes from baseline in triglycerides after treatment with LCQ908 monotherapy relative to fenofibrate or fish oil at 6 weeks |  | Baseline, 6 weeks | 
| Change from baseline in triglycerides after treatment with LCQ908 monotherapy relative to placebo at 12 weeks |  | Baseline, 12 weeks | 
| Number of patients in LCQ908 monotherapy with adverse events , serious adverse events and death |  | 12 weeks | 
| changefrom baseline in lipids and lipoprotein profiles |  | Baseline, 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypertriglyceridemia, Non familial Chylocmicronemia Syndrome (non-FCS)