Extension to a Randomized, Double-blind, Placebo Controlled Study of LCQ908 in Subjects With Familial Chylomicronemia Syndrome.

Study Overview
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Brief Summary
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This study was to determine long-term safety and tolerability, and continued efficacy in lowering triglycerides of LCQ908 in subjects with Familial Chylomicronemia Syndrome (FCS) (HLP type I).

Detailed Description
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This study was an 52 weeks open label extension starting at the lowest treatment dose used in CLCQ908B2302/NCT01514461 (i.e., 10 mg) with optional up-titrations, to evaluate the overall long-term safety and tolerability of LCQ908 in patients with Familial Chylomicronemia Syndrome, who either discontinued from the CLCQ908B2302/NCT01514461 study (due to tolerability issues) or completed the CLCQ908B2302/NCT01514461 study after 52 weeks. In addition, patients who had previously completed study CLCQ908A2212/NCT01146522 were eligible to participate. Following Protocol amendment 2, the original 52 week duration of this study (CLCQ908B2305) became Part A of LCQ908B2305 and a 78 week extension became Part B. However, following Protocol amendment 3, Part B was ended at the same time as the last patient of Part A completed 52 weeks. The reason for termination of Part B was the findings from the December 2014 interim analysis which suggested that the size of benefit that was anticipated from continued participation of patients in the 18 month extension trial (Part B) no longer supported trial extension beyond Part A.

Official Title
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An Open Label, 52-week, Safety and Tolerability Extension to a Randomized, Double-blind, Placebo Controlled Study of LCQ908 in Subjects With Familial Chylomicronemia Syndrome.

Conditions
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Familial Chylomicronemia Syndrome (FCS) (HLP Type I)

Intervention / Treatment
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* Drug: LCQ908


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent must be obtained before any assessment is performed. Subjects that either discontinue prematurely or complete the CLCQ908B2302 study after 52 weeks or FCS subjects who have previously completed study CLCQ908A2212. Exclusion Criteria: Subjects discontinued from the CLCQ908B2302 study for serious, potentially study drug related adverse events. Subjects from the CLCQ908B2302 study who have developed any other contraindication to participation (for example, renal failure) 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. 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. Subjects with type 1 diabetes mellitus or type 2 diabetes mellitus if HbA1C is ≥ 8.5%. Treatment with fish oil preparations within 4 weeks prior to randomization. Treatment with bile acid binding resins (i.e., colesevelam, etc) within 4 weeks prior to randomization. Treatment with fibrates within 8 weeks prior to randomization. Washout may occur following screening if required. Glybera [alipogene tiparvovec (AAV1-LPLS447X )] gene therapy exposure within the two years prior to screening. eGFR <45 ml/min/1.73m2 or history of chronic renal disease. 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LCQ908<br>Patients initiated at 10 mg/day. After at least 8 weeks of treatment with a dose, optional up-titration to the next possible dose will be allowed. One down titration allowed from the highest dose attained. | Drug: LCQ908<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Any Adverse Events, Serious Adverse Events and Death |  | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes From Baseline in Triglyceride Levels up to 52 Weeks | Blood samples were collected for a fasting lipid panel, including total triglycerides. Lipid measurements were collected after a 12 hour (overnight) fast. The maintenance of effect was assessed on triglyceride levels during continued therapy with LCQ908 for up to 52 weeks. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100. | Baseline, Week 12, 24 and 52 | 
| Changes From Baseline in Cholesterol Levels up to 52 Weeks | Blood samples were collected for a fasting lipid panel, including cholesterol level. Lipid measurements were collected after a 12 hour (overnight) fast. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100. | Baseline, Week 12, 24 and 52 | 
| Changes From Baseline in HDL and Non HDL Cholesterol Levels up to 52 Weeks | Blood samples were collected for a fasting lipid panel, including HDL and non HDL cholesterol level. Lipid measurements were collected after a 12 hour (overnight) fast. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100. | Baseline, Week 12, 24 and 52 | 
| Changes From Baseline in Glycerol Levels up to 52 Weeks | Blood samples were collected for a fasting lipid panel, including glycerol level. Lipid measurements were collected after a 12 hour (overnight) fast. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100. | Baseline, Week 12, 24 and 52 | 
| Changes From Baseline in Free Fatty Acid Levels up to 52 Weeks | Blood samples were collected for a fasting lipid panel, including free fatty acid level. Lipid measurements were collected after a 12 hour (overnight) fast. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100. | Baseline, Week 12, 24 and 52 | 
| Changes From Baseline in Apolipoprotein A1 Levels up to 52 Weeks | Fasting blood samples were collected by direct venipuncture or an indwelling cannula to evaluate the drug effect on lipoprotein biomarkers such as Apolipoprotein A1. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100. | Baseline, Week 12, 24 and 52 | 
| Changes From Baseline in Apolipoprotein B-48 Levels up to 52 Weeks | Fasting blood samples were collected by direct venipuncture or an indwelling cannula to evaluate the drug effect on lipoprotein biomarkers such as Apolipoprotein B-48. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100. | Baseline, Week 12, 24 and 52 | 
| Changes From Baseline in Apolipoprotein B-100 Levels up to 52 Weeks | Fasting blood samples were collected by direct venipuncture or an indwelling cannula to evaluate the drug effect on lipoprotein biomarkers such as Apolipoprotein B-100. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100. | Baseline, Week 12, 24 and 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Familial Chylomicronemia Syndrome (FCS) (HLP type I), LCQ908