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

Phase 3TerminatedNCT01589237

Novartis Pharmaceuticals38 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Familial Chylomicronemia Syndrome (FCS) (HLP Type I)

Interventions

LCQ908DRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Written informed consent must be obtained before any assessment is performed. 2. Subjects that either discontinue prematurely or complete the CLCQ908B2302 study after 52 weeks or FCS subjects who have previously completed study CLCQ908A2212. Exclusion Criteria: 1. Subjects discontinued from the CLCQ908B2302 study for serious, potentially study drug related adverse events. 2. Subjects from the CLCQ908B2302 study who have developed any other contraindication to participation (for example, renal failure) 3. 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. 4. 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. 5. Subjects with type 1 diabetes mellitus or type 2 diabetes mellitus if HbA1C is ≥ 8.5%. 6. Treatment with fish oil preparations within 4 weeks prior to randomization. 7. Treatment with bile acid binding resins (i.e., colesevelam, etc) within 4 weeks prior to randomization. 8. Treatment with fibrates within 8 weeks prior to randomization. Washout may occur following screening if required. 9. Glybera \[alipogene tiparvovec (AAV1-LPLS447X )\] gene therapy exposure within the two years prior to screening. 10. eGFR \<45 ml/min/1.73m2 or history of chronic renal disease. Other protocol defined inclusion/exclusion criteria may apply.

Locations (10)

Novartis Investigative Site

Seatlle, Washington, United States

Novartis Investigative Site

Chicoutimi, Quebec, Canada

Novartis Investigative Site

Ste-Foy, Quebec, Canada

Novartis Investigative Site

Outcomes

Primary Outcomes

Number of Patients With Any Adverse Events, Serious Adverse Events and Death

Time frame: 52 weeks

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Data from ClinicalTrials.gov

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